Secreted protein HFEAF41

ABSTRACT

The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

[0001] This application is a continuation-in-part of, and claims benefitunder 35 U.S.C. § 120 of U.S. patent application Ser. No:PCT/US98/05311, filed Mar. 19, 1998, which is hereby incorporated byreference, which claims benefit under 35 U.S.C. § 119(e) based on U.S.Provisional Applications: Filing Date Appln No. 1. 21-Mar-199760/041,277 2. 21-Mar-1997 60/042,344 3. 21-Mar-1997 60/041,276 4.21-Mar-1997 60/041,281 5. 30-May-1997 60/048,094 6. 30-May-199760/048,350 7. 30-May-1997 60/048,188 8. 30-May-1997 60/048,135 9.30-May-1997 60/050,937 10. 30-May-1997 60/048,187 11. 30-May-199760/048,099 12. 30-May-1997 60/048,352 13. 30-May-1997 60/048,186 14.30-May-1997 60/048,069 15. 30-May-1997 60/048,095 16. 30-May-199760/048,131 17. 30-May-1997 60/048,096 18. 30-May-1997 60/048,355 19.30-May-1997 60/048,160 20. 30-May-1997 60/048,351 21. 30-May-199760/048,154 22. 05-Aug-1997 60/054,804 23. 19-Aug-1997 60/056,370 24.02-Oct-1997 60/060,862

FIELD OF THE INVENTION

[0002] This invention relates to newly identified polynucleotides andthe polypeptides encoded by these polynucleotides, uses of suchpolynucleotides and polypeptides, and their production.

BACKGROUND OF THE INVENTION

[0003] Unlike bacterium, which exist as a single compartment surroundedby a membrane, human cells and other eucaryotes are subdivided bymembranes into many functionally distinct compartments. Eachmembrane-bounded compartment, or organelle, contains different proteinsessential for the function of the organelle. The cell uses “sortingsignals,” which are amino acid motifs located within the protein, totarget proteins to particular cellular organelles

[0004] One type of sorting signal, called a signal sequence, a signalpeptide, or a leader sequence, directs a class of proteins to anorganelle called the endoplasmic reticulum (ER). The ER separates themembrane-bounded proteins from all other types of proteins. Oncelocalized to the ER, both groups of proteins can be further directed toanother organelle called the Golgi apparatus. Here, the Golgidistributes the proteins to vesicles, including secretory vesicles, thecell membrane, lysosomes, and the other organelles.

[0005] Proteins targeted to the ER by a signal sequence can be releasedinto the extracellular space as a secreted protein. For example,vesicles containing secreted proteins can fuse with the cell membraneand release their contents into the extracellular space—a process calledexocytosis. Exocytosis can occur constitutively or after receipt of atriggering signal. In the latter case, the proteins are stored insecretory vesicles (or secretory granules) until exocytosis istriggered. Similarly, proteins residing on the cell membrane can also besecreted into the extracellular space by proteolytic cleavage of a“linker” holding the protein to the membrane.

[0006] Despite the great progress made in recent years, only a smallnumber of genes encoding human secreted proteins have been identified.These secreted proteins include the commercially valuable human insulin,interferon, Factor VIII, human growth hormone, tissue plasminogenactivator, and erythropoeitin. Thus, in light of the pervasive role ofsecreted proteins in human physiology, a need exists for identifying andcharacterizing novel human secreted proteins and the genes that encodethem. This knowledge will allow one to detect, to treat, and to preventmedical disorders by using secreted proteins or the genes that encodethem.

SUMMARY OF THE INVENTION

[0007] The present invention relates to novel polynucleotides and theencoded polypeptides. Moreover, the present invention relates tovectors, host cells, antibodies, and recombinant methods for producingthe polypeptides and polynucleotides. Also provided are diagnosticmethods for detecting disorders related to the polypeptides, andtherapeutic methods for treating such disorders. The invention furtherrelates to screening methods for identifying binding partners of thepolypeptides.

DETAILED DESCRIPTION

[0008] Definitions

[0009] The following definitions are provided to facilitateunderstanding of certain terms used throughout this specification.

[0010] In the present invention, “isolated” refers to material removedfrom its original environment (e.g., the natural environment if it Isnaturally occurring), and thus is altered “by the hand of man” from itsnatural state. For example, an isolated polynucleotide could be part ofa vector or a composition of matter, or could be contained within acell, and still be “isolated” because that vector, composition ofmatter, or particular cell is not the original environment of thepolynucleotide.

[0011] In the present invention, a “secreted” protein refers to thoseproteins capable of being directed to the ER, secretory vesicles, or theextracellular space as a result of a signal sequence, as well as thoseproteins released into the extracellular space without necessarilycontaining a signal sequence. If the secreted protein is released intothe extracellular space, the secreted protein can undergo extracellularprocessing to produce a “mature” protein. Release into the extracellularspace can occur by many mechanisms, including exocytosis and proteolyticcleavage.

[0012] As used herein, a “polynucleotide” refers to a molecule having anucleic acid sequence contained in SEQ ID NO:X or the cDNA containedwithin the clone deposited with the ATCC. For example, thepolynucleotide can contain the nucleotide sequence of the full lengthcDNA sequence, including the 5′ and 3′ untranslated sequences, thecoding region, with or without the signal sequence, the secreted proteincoding region, as well as fragments, epitopes, domains, and variants ofthe nucleic acid sequence. Moreover, as used herein, a “polypeptide”refers to a molecule having the translated amino acid sequence generatedfrom the polynucleotide as broadly defined.

[0013] In the present invention, the full length sequence identified asSEQ ID NO:X was often generated by overlapping sequences contained inmultiple clones (contig analysis). A representative clone containing allor most of the sequence for SEQ ID NO:X was deposited with the AmericanType Culture Collection (“ATCC”). As shown in Table 1, each clone isidentified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number.The ATCC is located at 10801 University Boulevard. Manassas, Va.20110-2209, USA. The ATCC deposit was made pursuant to the terms of theBudapest Treaty on the international recognition of the deposit ofmicroorganisms for purposes of patent procedure.

[0014] A “polynucleotide” of the present invention also includes thosepolynucleotides capable of hybridizing, under stringent hybridizationconditions, to sequences contained in SEQ ID NO:X, the complementthereof, or the cDNA within the clone deposited with the ATCC.“Stringent hybridization conditions” refers to an overnight incubationat 42° C. in a solution comprising 50% formamide, 5×SSC (750 mM NaCl, 75mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt'ssolution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmonsperm DNA, followed by washing the filters in 0.1×SSC at about 65° C.

[0015] Also contemplated are nucleic acid molecules that hybridize tothe polynucleotides of the present invention at lower stringencyhybridization conditions. Changes in the stringency of hybridization andsignal detection are primarily accomplished through the manipulation offormamide concentration (lower percentages of formamide result inlowered stringency); salt conditions, or temperature. For example, lowerstringency conditions include an overnight incubation at 37° C. in asolution comprising 6×SSPE (20×SSPE=3M NaCl; 0.2M NaH₂PO₄; 0.02M EDTA,pH 7.4), 0.5% SDS, 30% formamide, 100 μg/ml salmon sperm blocking DNA;followed by washes at 50° C. with 1×SSPE, 0.1% SDS. In addition, toachieve even lower stringency, washes performed following stringenthybridization can be done at higher salt concentrations (e.g. 5×SSC).

[0016] Note that variations in the above conditions may be accomplishedthrough the inclusion and/or substitution of alternate blocking reagentsused to suppress background in hybridization experiments. Typicalblocking reagents include Denhardt's reagent, BLOTTO, heparin, denaturedsalmon sperm DNA, and commercially available proprietary formulations.The inclusion of specific blocking reagents may require modification ofthe hybridization conditions described above, due to problems withcompatibility.

[0017] Of course, a polynucleotide which hybridizes only to polyA+sequences (such as any 3′ terminal poly(A) tract of a cDNA shown in thesequence listing), or to a complementary stretch of T (or U) residues,would not be included in the definition of “polynucleotide,” since sucha polynucleotide would hybridize to any nucleic acid molecule containinga poly (A) stretch or the complement thereof (e.g., practically anydouble-stranded cDNA clone).

[0018] The polynucleotide of the present invention can be composed ofany polyribonucleotide or polydeoxribonucleotide, which may beunmodified RNA or DNA or modified RNA or DNA. For example,polynucleotides can be composed of single- and double-stranded DNA, DNAthat is a mixture of single- and double-stranded regions, single- anddouble-stranded RNA, and RNA that is mixture of single- anddouble-stranded regions, hybrid molecules comprising DNA and RNA thatmay be single-stranded or, more typically, double-stranded or a mixtureof single- and double-stranded regions. In addition, the polynucleotidecan be composed of triple-stranded regions comprising RNA or DNA or bothRNA and DNA. A polynucleotide may also contain one or more modifiedbases or DNA or RNA backbones modified for stability or for otherreasons. “Modified” bases include, for example, tritylated bases andunusual bases such as inosine. A variety of modifications can be made toDNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically,or metabolically modified forms.

[0019] The polypeptide of the present invention can be composed of aminoacids joined to each other by peptide bonds or modified peptide bonds,i.e., peptide isosteres, and may contain amino acids other than the 20gene-encoded amino acids. The polypeptides may be modified by eithernatural processes, such as posttranslational processing, or by chemicalmodification techniques which are well known in the art. Suchmodifications are well described in basic texts and in more detailedmonographs, as well as in a voluminous research literature.Modifications can occur anywhere in a polypeptide, including the peptidebackbone, the amino acid side-chains and the amino or carboxyl termini.It will be appreciated that the same type of modification may be presentin the same or varying degrees at several sites in a given polypeptide.Also, a given polypeptide may contain many types of modifications.Polypeptides may be branched, for example, as a result ofubiquitination, and they may be cyclic, with or without branching.Cyclic, branched, and branched cyclic polypeptides may result fromposttranslation natural processes or may be made by synthetic methods.Modifications include acetylation, acylation, ADP-ribosylation,amidation, covalent attachment of flavin, covalent attachment of a hememoiety, covalent attachment of a nucleotide or nucleotide derivative,covalent attachment of a lipid or lipid derivative, covalent attachmentof phosphotidylinositol, cross-linking, cyclization, disulfide bondformation, demethylation, formation of covalent cross-links, formationof cysteine, formation of pyroglutarmate, formylation,gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation,iodination, methylation, myristoylation, oxidation, pegylation,proteolytic processing, phosphorylation, prenylation, racemization,selenoylation, sulfation, transfer-RNA mediated addition of amino acidsto proteins such as arginylation, and ubiquitination. (See, forinstance, PROTEINS—STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E.Creighton, W. H. Freeman and Company, New York (1993); POSTTRANSLATIONALCOVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press,New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646(1990); Rattan et al., Ann NY Acad Sci 663:48-62 (1992).)

[0020] “SEQ ID NO:X” refers to a polynucleotide sequence while “SEQ IDNO:Y” refers to a polypeptide sequence, both sequences identified by aninteger specified in Table 1.

[0021] “A polypeptide having biological activity” refers to polypeptidesexhibiting activity similar, but not necessarily identical to, anactivity of a polypeptide of the present invention, including matureforms, as measured in a particular biological assay, with or withoutdose dependency. In the case where dose dependency does exist, it neednot be identical to that of the polypeptide, but rather substantiallysimilar to the dose-dependence in a given activity as compared to-thepolypeptide of the present invention (i.e., the candidate polypeptidewill exhibit greater activity or not more than about 25-fold less and,preferably, not more than about tenfold less activity, and mostpreferably, not more than about three-fold less activity relative to thepolypeptide of the present invention.)

Polynucleotides and Polypeptides of the Invention

[0022] Features of Protein Encoded by Gene No: 1

[0023] The translation product of this gene shares sequence homologywith nucleolin, which is thought to be important in macromoleculebinding, as well as some membrane proteins. Preferred polypeptidefragments comprise the amino acid sequence:DPEAADSGEPQNKRTPDLPEEEYVKEEIQENEEAVKDILVEATREFEEVVVDES (SEQ ID NO:231);QKLKRKAEEDPEAADSGEPQNKRTDLPEEYVKEEIQENEE AVKILVEATREFEENNVDES (SEQ IDNO:232); KAIEKSSLTQHSWQSLKDRYLKHLRCQEHKYLLGDAPVSPSSQKLKRKAEEDPEAADSGEPQNKRTDLPEEEYVKEEIQNEEAVKKMLVEATREFEEVVVDESPPDFEIHI (SEQ ID NO:233). Also preferredare the polynucleotide fragments encoding these polypeptide fragments.This gene maps to chromosome 16, and therefore can be used as a markerin linkage analysis for chromosome 16.

[0024] This gene is expressed primarily in brain and kidney and to alesser extent in wide range of tissues.

[0025] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,cell-cell interaction or cell-matrix interaction. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the brain and kidney, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., brain and other tissueof the nervous system, and kidney, and cancerous and wounded tissues) orbodily fluids (e.g. serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO.121 as residues: Met-1 toTrp-10.

[0026] The tissue distribution in brain and kidney combined with thehomology to nucleolin indicates that polynucleotides and polypeptidescorresponding to this gene are useful for treatment/diagnosis ofdiseases involving cell-cell interaction or cell-extracellular matrixinteraction. Protein, as well as, antibodies directed against theprotein may show utility as a tissue-specific marker and/orimmunotherapy target for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:11 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1665 of SEQ ID NO:11, b is aninteger of 15 to 1679, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID. NO:11, and where the b is greaterthan or equal to a+14.

[0027] Features of Protein Encoded by Gene No: 2

[0028] The translation product of this gene shares sequence homologywith a porcine zona pellucida protein ZPDS. 1711. (See Accession No.R39356.) These two proteins have weak homology with Drosophilacornissureless and metal homeostasis proteins which are thought to beimportant in controlling growth cone guidance across the CNS midline andprotecting cells against reactive oxygen toxicity. Thus, based onhomology, it is likely that this gene may also be involved indevelopment. Preferred polypeptide fragments comprise the amino acidsequence: LPSYDEAERTYEATIPLVPGRDEDFVGRDDFDDADQLRIGNDGIFMLTFFMAFLFNWIGFFLSFCLTTSAAGRYGAISGFGLSLIKWILIVRFSTYFPGYFDGQYWLWWVFLVLGLLFLRGFINYAKVRKM PETFSNLPRTRVLFI(SEQ ID NO:234); and/or AGRYGAISGFGLSLIKWILIVRFS (SEQ ID NO:235). Alsopreferred are polynucleotide fragments encoding these polypeptidefragments. The gene that encodes the disclosed cDNA is thought to resideon chromosome 5. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 5.

[0029] This gene is expressed primarily in kidney, adrenal gland, brain,fetal and reproductive tissues, and to a lesser extent in wide range oftissues.

[0030] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,fertilization control or tissue damage by metabolites or other toxicagents. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thereproductive, urogenital or renal system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. reproductive, kidney, adrenal gland,and brain and other tissue of the nervous system, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, amniotic fluid, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0031] The tissue distribution in reproductive tissues combined with thehomology to zona pellucida protein indicates that polynucleotides andpolypeptides corresponding to this gene are useful for fertility controlsuch as contraceptive development. The homology with metal homeostasisand cornissureless genes indicates the gene's function in spermatozoaguidance and protection. It would also be useful for thetreatment/diagnosis of tissue damages caused by toxic metabolites andother agents since the gene product is also expressed in urosecretivetissues. Protein, as well as, antibodies directed against the proteinmay show utility as a tissue-specific marker and/or immunotherapy targetfor the above listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:12 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1949 of SEQ ID NO:12, b is an integer of 15 to1963, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:12, and where the b is greater than or equalto a+14.

[0032] Features of Protein Encoded by Gene No: 3

[0033] This gene is expressed primarily in liver and to a lesser extentin placenta. Preferred polypeptide fragments comprise the amino acidsequence: MKHLSAWNFT KLTFLWLWEIFEGSVENCQTLTSYSKLQIKYTFSRGSTFYI (SEQ IDNO:236). Also preferred are polynucleotide fragments encoding thesepolypeptide fragments.

[0034] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,digestive, metabolic, developmental, and nutrient transport/utilizationdisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thedigestive and circulatory system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., liver, and placenta, and cancerousand wounded tissues) or bodily fluids (e.g., amniotic fluid, lymph,bile, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0035] The tissue distribution in liver and placenta indicates that theprotein product is either an extracellular enzyme or a molecule carrier.Therefore, polynucleotides and polypeptides corresponding to this geneare useful for diagnosis/treatment of digestive and nutrienttransport/utilization disorders, including malabsorption andmalnutrition. Protein, as well as, antibodies directed against theprotein may show utility as a tissue-specific marker and/orimmunotherapy target for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:13 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1198 of SEQ ID NO:13, b is aninteger of 15 to 1212, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:13, and where the b is greaterthan or equal to a+14.

[0036] Features of Protein Encoded by Gene No: 4

[0037] This gene shares homology with the sap47 gene of Drosophilamelcunogasrer, a gene which codes for a conserved neuronal proteinassociated with synaptic terminals. (See Mol. Brain Res. 32:45-54(1995); see also, Accession No. 929571.) Thus, based on homology, thegene of the present invention also should be associated with synapticterminals. Preferred polypeptide fragments comprise the amino acidsequence: FSSDFRTSPWESRRVESKKTSARCGLWGSGPRRRPASGMFRGLSSWLGLQQPVAGGGQPNGDAPPEQPSETVAESAEEELQQAGDQELLHQAKDFGNYLFNFASAATKKITESVAETAQTIKKSVEECKIDGIIDKTIIGDFQQKEQVEEQHTKKSEAAVPPWVDTNDEETIQQQILALSADKRNFLRDPPAGVQFNFDFDQMYPVALVML (SEQ ID NO:237);MRFALVPKLVKEEVPWRNYFYRVSLIKQSAQLTALAAQQQA AGKGGEEQ (SEQ ID NO:238);STSPGVSEFVSDAFDACNLNQEDLRKENIEQLVLDKKQEETAVLEEDSADWEKELQQELQEYEVVTESEKRDEiNWVDK (SEQ ID NO:239);SPWESRRVESKATSARCGLWGSGPRRRPASGMFRGLSSWLGLQQ PVAGGGQPNGDAPPEQPS (SEQ IDNO:240); PVAGGGQPNGDAPPEQPSETV ESAEEELQQAGDQELLHQAKDFGNYLENASAATKlTESVAE(SEQ ID NO: 241); and/or FQKEQKVEEQHTKKSEAAVPPWDTNDEETIQQILALSADKRNFLRDPPAGVQFNFDFDQMYPVALVML (SEQ ID NO:242). Also preferred arepolynucleotide fragments encoding these polypeptide fragments. Contactof cells with supernatant expressing the product of this gene increasesthe permeability of the plasma membrane of aortic smooth muscle cells tocalcium. Thus, it is likely that the product of this gene is involved ina signal transduction pathway that is initiated when the product binds areceptor on the surface of the aortic smooth muscle cells. Thus,polynucleotides and polypeptides have uses which include, but are notlimited to, activating aortic smooth muscle cells.

[0038] This gene is expressed primarily in kidney pyramids and to alesser extent in lung and other tissues of various types. This genefluxes calcium in human aortic smooth muscle cells, and therefore isinvolved in signal transduction.

[0039] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, renal,developmental, vascular, and nervous disorders. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the kidney and/or s system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., kidney, lung, brain and othertissue of the nervous system, developmental, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma,urine, synovial fluid or spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0040] The tissue distribution in kidney and lung and homology withsap47 indicates that the protein product has regulatory or directfunctions in molecular exchange with body fluids and nervous systemsignaling. Polynucleotides and polypeptides corresponding to this geneare useful for treatment of disorders in kidney and nervous system. Theactivity of the translation product of this gene in activating aorticsmooth muscle cells supports the notion that this protein is involved inregulatory or direct functions in molecular exchange with body fluids.This clone would be useful for the diagnosis and treatment of disordersin kidney and the nervous system. Protein, as well as, antibodiesdirected against the protein may show utility as a tissue-specificmarker and/or immunotherapy target for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:14 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 2047 of SEQID NO:14, b is an integer of 15 to 2061, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:14, and wherethe b is greater than or equal to a+14.

[0041] Features of Protein Encoded by Gene No: 5

[0042] The translation product of this gene shares sequence homologywith the mouse Ly-9.2 antigen which is thought to be an important cellsurface marker in lymphoids, myeloids and hematopoietic progenitors.(See Accession No. gil191932.) Preferred polypeptide fragments comprisethe amino acid sequence: PFICVARPVSRNFSSPI LARKLCEGAA (SEQ ID NO:243);and/or KEDPANTVYSTVEIPKKMIENPHSLLT MPDTPRL (SEQ ID NO:244). Alsopreferred are polynucleotide fragments encoding these polypeptidefragments. Based on homology, it is likely that this gene is also a cellsurface marker, involved in hematopoiesis.

[0043] This gene is expressed primarily in activated macrophages,monocytes and T-cells and to a lesser extent in spleen and bone marrow.

[0044] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immuneand hematopoletic disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune and hematopoletic systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. immune, blood cells, and bonemarrow, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not having,the disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO. 125 as residues: Lys-26 to Tyr-33, Arg-44 to Ele-49,Ser-53 to Lys-71, Lys-86 to Pro-91.

[0045] The tissue distribution in immune tissue combined with thehomology to a protein within the Ly-9.2 surface immunoglobulin familyindicates that polynucleotides and polypeptides corresponding to thisgene are useful for diagnosis of immune and hematopoletic disorders.Polypeptides and polynucleotides corresponding to this gene are also beused as a marker for leukemia or a modulator of the functions of thecells of macrophagelmonocyte or T-cell types. Expression of this geneproduct in immune cells suggests a role in the regulation of theproliferation; survival; differentiation; and/or activation ofpotentially all hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, leukemia,rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, andpsoriasis. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:15 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1398 of SEQ ID NO:15, b is an integer of 15 to1412, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:15, and where the b is greater than or equalto a+14.

[0046] Features of Protein Encoded by Gene No: 6

[0047] The translation product of this gene shares sequence homologywith the Drosophila glutactin gene which is thought to be important incell-cell interaction or celi-extracellular matrix contact. The geneencoding the disclosed cDNA is thought to region chromosome 16.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 16.

[0048] This gene is expressed primarily in colon tissue, aortaendothelia cells and to a lesser extent in skin, breast tissue andT-cells.

[0049] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of these tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, diseasesof the gastrointestinal tract, vascular system or T-cell development.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of these tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the digestivesystem, cardiovascular system, and immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., colon, endothelial,cardiovascular tissue, skin, mammary tissue, and blood cells, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, breastmilk, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0050] The tissue distribution and homology to glutactin indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the development and maintenance of the integrity of the basalmembrane in the gastrointestinal tract, or vasculature in thecardiovascular system. The expression in T-cells also indicates theprotein may be involved in T-cell adhesion, cell-cell interaction anddevelopment. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:16 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1038 of SEQ ID NO:16, b is an integer of 15 to1052, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:16, and where the b is greater than or equalto a+14.

[0051] Features of Protein Encoded by Gene No: 7

[0052] The translation product of this gene shares sequence homologywith MURF4 protein, an ATPase homolog, which is thought to be importantin ATP hydrolysis.

[0053] This gene is expressed primarily in breast tissue.

[0054] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, breastcancer and non-neoplastic breast diseases. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of these tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the breast tissue, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., mammary tissue, and cancerous andwounded tissues) or bodily fluids (e.g., breast milk, lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0055] The tissue distribution in breast tissue combined with thehomology to the MURF4 gene indicates that polynucleotides andpolypeptides corresponding to this gene are useful for diagnosis andtreatment of neoplastic or non-neoplastic breast diseases because ATPaselike protein may be involved in changed metabolic states of the breast.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:17 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 669 of SEQ ID NO:17, b is an integer of 15 to 683, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:17, and where the b is greater than or equal to a+14.

[0056] Features of Protein Encoded by Gene No: 8

[0057] This gene shares homology to the alcohol dehydrogenase gene.Preferred polypeptide fragments comprise the amino acid sequence:ASAVLLDLPNSG GEAQAKKLGNNCVFAPADVTSEKDVQTALALAKGGRVDVAVNCAGLkVASKTYNLKKGQTHTLEDFQRVLDVNLMGTFNIRVAGEIVIGQNEPDQGGQRGVIINTASVAAEGQVGQAAYSASKGGIVGMTLPIARDLAPIGIRVMITIAPGLFGTPLLTSLPEKVCNFLASQVPFPSRLGDPAEYABLVQAIENPFLNGEVIRLDGAIRMQ P (SEQ IDNO:245); SVAAFEGQVGQAAYSASKGGIVGOITLPIA (SEQ ID NO:246). and/orSVAAFEGQVGQAAYSASKGGIVGMITLPIA (SEQ ID NO:247). Polynucleotides encodingthese fragments are also encompassed by the invention. Other groups havealso recently cloned this gene, recognizing its homology to alcoholdehydrogenase. (See Accession No. 1778355.) Moreover, a second grouprecently cloned the mouse homologue of this gene. (See Accession No.2078284.) They found that the mouse homologue binds to amyloidbeta-peptide and mediates neurotoxicity in Alzheimer's disease, callingthe protein ERAB. This gene maps to chromosome X, and therefore can beused in linkage analysis as a marker for chromosome X. Therefore,mutations in the translated product of this gene may be involved inAlzheimer's disease in humans, as well as other sex linked diseases.This gene can be used as a diagnostic marker for these diseases.

[0058] It has been discovered that this gene is expressed primarily inbreast cancer tissue, infant brain, and to a lesser extent in fetalliver tissue.

[0059] Therefore, nucleic acids of the invention are useful as reagentsfor differential identification of the tissue(s) or cell type(s) presentin a biological sample and for diagnosis of the following diseases andconditions: neurodegenerative diseases, breast cancer, non-neoplasticbreast diseases, or developmental disorders. Similarly, polypeptides andantibodies directed to those polypeptides are useful to provideimmunological probes for differential identification of these tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the brain and CNS, and breast tissue, expressionof this gene at significantly higher or lower levels may be detected incertain tissues or cell types (e.g. brain, breast, metabolic,developmental, immune, hematopoietic, cancerous and wounded tissues) orbodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine,synovial fluid or spinal fluid) taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue from an individual not having thedisorder. Preferred epitopes include those comprising a sequence shownin SEQ ID NO:128 as residues: Arg-45 to Ser-53.

[0060] The tissue distribution in neural tissue combined with thehomology to the ERAB mouse gene suggests that the protein product ofthis clone would be useful for the diagnosis and treatment of Alzheimersand related neurodegenerative diseases. Mutations in the translatedproduct of this gene may be involved in Alzheimer's disease in humans,as well as other sex linked diseases. This gene can be used as adiagnostic marker for these diseases. Furthermore, the tissuedistribution suggests that this gene may also be involved in neoplasticor non-neoplastic breast diseases in humans. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:18 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1040 of SEQID NO:18, b is an integer of 15 to 1054, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:18, and wherethe b is greater than or equal to a+14.

[0061] Features of Protein Encoded by Gene No: 9

[0062] The translation product of this gene shares week sequencehomology with rat N-methyl-D-aspartate receptor subunit and otherproline-rich proteins which are thought to be important inneurotransmission or protein-protein intereaction.

[0063] This gene is expressed primarily in synovial hypoxia and to alesser extent in ovary, senescent cells and brain.

[0064] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, synovialhypoxia, reproductive, or neural disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the synovial and brain, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., synovial tissue, ovary and otherreproductive tissue, and brain and other tissue of the nervous system,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0065] The tissue distribution in synovial hypoxia and nerve tissues,and homology to N-methyl-D-aspartate receptor subunit and otherproline-rich proteins indicates that polynucleotides and polypeptidescorresponding to this gene are useful for diagnosis and intervention ofsynovial hypoxia and other synovial disorders, particularly disordersinvolving nitric oxide signaling. Protein, as well as, antibodiesdirected against the protein may show utility as a tissue-specificmarker and/or immunotherapy target for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:19 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1379 of SEQID NO:19, b is an integer of 15 to 1393, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:19, and wherethe b is greater than or equal to a+14.

[0066] Features of Protein Encoded By Gene No: 10

[0067] This gene is expressed primarily in prostate and keratinocytes,and to a lesser extent in placenta, ovary and primary dendritic cells.

[0068] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, male andfemale infertility, cancer, skin disorders, and other hyperproliferativedisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of these tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thereproductive system, skin, and neopiasia, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., prostate, skin, placenta, ovary andother reproductive tissue, and cancerous and wounded tissues) or bodilyfluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO. 130 as residues:Pro-17 to Met-23, Ala-30 to Trp-3S, Ile-49 to Trp-54, Lys-68 to Gly-74,Thr-93 to Gly-99, Met-126 to Glu-132, Gly-173 to Ser-178, Lys-205 toTyr-214.

[0069] The tissue distribution of this gene in the prostate, placentaand ovary indicates that this gene product is useful fortreatment/diagnosis of male or female infertility, endocrine disorders,fetal deficiencies, ovarian failure, amenorrhea, ovarian cancer, benignprostate hyperplasia, prostate cancer, and other forms of cancer of thereproductive system. The tissue distribution also suggests that theprotein product of this clone would be useful for the treatment,diagnosis, and/or prevention of various skin disorders includingcongenital disorders (i.e. nevi, moles, freckles, Mongolian spots,hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses,Bowen's disease, basal cell carcinoma, squamous cell carcinoma,malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi'ssarcoma), injuries and inflammation of the skin (i.e. wounds, rashes,prickly heat disorder, psoriasis, dermatitis), atherosclerosis,uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupuserythematosus, vitiligo, dermatomyositis, morphea, scleroderma,pemphigoid, and pemphigus), keloids, striae, erythema, petechiae,purpura, and xanthelasma. Moreover, such disorders may predisposeincreased susceptibility to viral and bacterial infections of the skin(i.e. cold sores, wars, chickenpox, molluscum contagiosum, herpeszoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot,and ringworm). Protein, as well as, antibodies directed against theprotain may show utility as a tissue-specific marker and/orimmunotherapy target for the above-listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:20 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1201 of SEQ ID NO:20, b is aninteger of 15 to 1215, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:20, and where the b is greaterthan or equal to a+14.

[0070] Features of Protein Encoded by Gene No: 11

[0071] This gene is expressed primarily in the thyroid and to a lesserextent in the pineal gland. The gene encoding the disclosed cDNA isthought to reside on chromosome 10. Accordingly, polynucleotides relatedto this invention are useful as a marker in linkage analysis forchromosome 10. Preferred polypeptide fragments comprise the amino acidsequence: HPIEWAINAATLSQFY (SEQ ID NO:248); CWIKYCLTLMQN AQLSMQDNIG (SEQID NO:249); KVSYLRPLDFEEARELF LLGQHYVF (SEQ ID NO:250);MERRCKMHRXIAMLEPLTVDLNPQ (SEQ ID NO:251); and/or SHIV KKINLNKSALKYYQLFLD(SEQ ID NO:252). Also preferred are polynucleotides encoding thesepolypeptide fragments.

[0072] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immune,thyroid and pineal gland disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of these tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the immune and endocrine systems, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g. immune, thyroid andpineal gland, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:131 as residues: Ser-2 to Ser-8, Thr-38 to Arg-44.The tissue distribution indicates that polynucleotides and polypeptidescorresponding to this gene are useful for treating/detecting immunedisorders such as arthritis, asthma, immune deficiency diseases (e.g.,AIDS), and leukemia, as well as treating/detecting thymus disorders(e.g., Graves Disease, lymphocytic thyroiditis, hyperthyroidism, andhypothyroidism), and treating/detecting pineal gland disorders (e.g.,circadian rhythm disturbances associated with shift work, jet lag,blindness, insomnia and old age). Protein, as well as, antibodiesdirected against the protain may show utility as a tissue-specificmarker and/or immunotherapy target for the above-listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:21 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 2028 of SEQID NO:21, b is an integer of 15 to 2042, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:21, and wherethe b is greater than or equal to a+14.

[0073] Features of Protein Encoded by Gene No: 12

[0074] The gene encoding the disclosed cDNA is thought to reside onchromosome 9. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 9.

[0075] It has been discovered that this gene is expressed primarily incolon and brain tissue, and to a lesser extent in lung and tonsils.

[0076] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,pulmonary or immune disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of these tissue(s) or celltype(s). For a number of disorders of the above tissues or cells,particularly of the pulmonary and immune systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., immune, brain, pulmonary tissue,and tonsils, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, pulmonary surfactant or sputum, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:132 as residues:Glu-28 to Gly-49.

[0077] The tissue distribution of this gene only in lung indicates thatit could play a role in the treatment/detection of lung lymphoma orsarcoma formation, pulmonary edema and embolism, bronchitis and cysticfibrosis. Its expression in tonsils indicates a potential role in thetreatment/detection of immune disorders such as arthritis, asthma,immune deficiency diseases (e.g., AIDS), and leukemia, in addition tothe treatment/detection of tonsillitis. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:22 and may have been publicly available prior to conception, ofthe present invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1858 of SEQ ID NO:22, b is aninteger of 15 to 1872, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:22, and where the b is greaterthan or equal to a+14.

[0078] Features of Protein Encoded by Gene No: 13

[0079] This gene is expressed primarily in progenitor cells (CD34 cells)of lymphoid, myeloid and erythroid cells.

[0080] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,hematopoletic and immune disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of these tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the hematopoietic and immune systems, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., immune, blood cells,myeloid cells, and bone marrow, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. The predominant tissue distributionof this gene in hematopoietic cell types indicates that the gene couldbe important for the treatment or detection of immune or hematopoieticdisorders including arthritis, asthma, immunodeficiency diseases andleukemia. Preferred embodiments of the present invention are polypeptidefragments comprising the amino acid sequence:FTHLSTCLLSLLLVRIMSGFLLLARASPSI CALDSSCFVYCSSYSSSCFLHQHfPSLLDHLCQ (SEQ IDNO:253); or FLLL ARASPSICALDSSCFVQEY (SEQ ID NO:254). Also preferred arepolynucleotide fragments encoding these polypeptide fragments. Protein,as well as, antibodies directed against the protain may show utility asa tissue-specific marker and/or immunotherapy target for theabove-listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:23 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 275 of SEQ ID NO:23, b is an integer of 15 to289, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:23, and where the b is greater than or equalto a+14.

[0081] Features of Protein Encoded by Gene No: 14

[0082] This gene is homologous to the Drosophila Regena (Rga) gene. (SeeAccession No. 1658504.) This Drosophila gene is thought to be a homologof the global negative transcriptional regulator NOT2 (CDC36) fromyeast, which modifies gene expression and suppresses position effectvariegation. Preferred polypeptide fragments comprise the amino acidsequence: PDGRVTNIPQGMVTDQFGMIIGLLTFIRAAETDPGMVHL ALGSDLTTLGLNLNS (SEQID NO:255); VHLALGSDLTTLGLNLNSPENLYP (SEQ ID NO:257);EDLLFYLYYGGDVLQLLAAVELFNRDWRYHKEERVWI TR (SEQ ID NO:256);EDLLFYLYMNGGDVLQLLAAVELFNRDWRYH KEERVWITR (SEQ ID NO:258); and/orHINEDFPALPGS (SEQ ID NO:259).

[0083] This gene is expressed primarily in placenta and to a lesserextent in infant brain.

[0084] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,neurodegenerative and developmental disorders. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the neurological system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., placenta, and brain and othertissue of the nervous system, reproductive, developmental tissues, andcancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:134 as residues: Leu-9 to Tyr-15, Asp-34 to Gln-46,Pro-51 to Asp-57, Gly-88 to Thr-104, Thr-123 to Ser-128.

[0085] The tissue distribution of this gene in neural tissue indicatesthat it could be used in the detection and/or treatment of neurologicaldisorders such as such as Alzheimer's Disease, Parkinson's Disease,Huntington's Disease, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder, and panic disorder. Similarly, expressionwithin fetal and other cellular sources marked by proliferating cells,combined with the homology to a transcriptional regulator suggests thatthis protein may play a role in the regulation of cellular division, andmay show utility in the diagnosis and treatment of cancer and otherproliferative disorders. Similarly, embryonic development also involvesdecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:24 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 3519 of SEQID NO:24, b is an integer of 15 to 3533, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:24, and wherethe b is greater than or equal to a+14.

[0086] Features of Protein Encoded by Gene No: 15

[0087] This gene is expressed primarily in adrenal land tumor andosteoclastoma.

[0088] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,endocrine and bone disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe endocrine system and in bone, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., adrenal gland, and bone, skeletaltissues, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:135 as residues: Ile-52 to Trp-57.

[0089] The tissue distribution of this gene in endocrine tissueindicates that it may be involved in the treatment and/or detection ofadrenal gland tumors, osteosarcomas, endocrine disorders and bonedisorders, particularly osteoporosis. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:25 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1134 of SEQ ID NO:25, b is aninteger of 15 to 1148, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:25, and where the b is greaterthan or equal to a+14.

[0090] Features of Protein Encoded by Gene No: 16

[0091] The translation product of this gene shares sequence homologywith the FK506 binding protein, a protein which plays an important rolein immunosupression. (See Accession No. M75099.) Specifically, a 12-kDaFK506-binding protein (FKBP-12) is a cytosolic receptor for theimmunosuppressants FK506 and rapamycin. (See, Proc. Natl. Acad. Sci. 88:6677-6681 (1991).) Thus, based on homology, it is likely that this genealso has immunosuppression activity or may be involved in otheractivities related to calcium dependent regulation. Preferredpolypeptides comprise the amino acid sequence:GRUDTSLTRDPLVIELGQKQVPGLEQSLLDMCVEKRRAIIPSHLAYGKRGFPPSVPADAVVQYDVFLIALIR (SEQ ID NO:260); and/or IHYTGSLV DGR IIDTS(SEQ ID NO:261): Also preferred are the polynucleotide fragmentsencoding these polypeptides.

[0092] This gene is expressed primarily in melanocytes. Furthermore,northern analysis demonstrated that this gene is also abundant in fetalliver and kidney. In adult tissues, it is expressed relatively highly inspleen, placenta, and thymus, and at a low level in other tissues.

[0093] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,developmental conditions, or cancer and other hyperproliferativedisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system and cancer, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g. immune, melanocytes, developmental, integumentary,hepatic, renal, and cancerous and wounded tissues) or bodily fluids(e.g., amniotic fluid, lymph, bile, serum, plasma, urine, synovial fluidor spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:136 as residues:Ala-118 to Phe-114, Ar-178 to Lys-201.

[0094] The tissue distribution in developing tissues combined with thehomology to the FK506 binding proteins which are believed to a role inimmunosupression mediated by the immunosupressant drugs rapamycin andcyclosporin, indicates that this gene could serve as a novel target forthe identification of novel immunosupressant drugs. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:26 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 703 of SEQID NO:26, b is an integer of 15 to 717, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:26, and wherethe b is greater than or equal to a+14.

[0095] Features of Protein Encoded by Gene No: 17

[0096] The translation product of this gene shares sequence homologywith the rat calcium-activated potassium channel rSK3, which is thoughtto be important in regulating vascular tone. (See Accession No.gil12564072, gil1575663, and gil1575661.) Although homologous to theseproteins, this gene contains an 18 amino acid insert, not previouslyidentified in the homologs. Preferred polypeptide fragments comprise theamino acid sequence: CESPESPAQPSGSSLPAWYH (SEQ ID NO:262). Alsopreferred are the polynucleotide fragments encoding these polypeptides.

[0097] This gene is expressed primarily in B-cells, frontal cortex andendothelial cells.

[0098] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immune,cardiovascular (hyperihypotension, asthma, pulmonary edema. pneumonia,heart disease, restenosis, atherosclerosis, stroke, angina andthrombosis) or neurological disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the cardiovascular and nervous systems, expression ofthis gene at significantly hither or lower levels may be routinelydetected in certain tissues or cell types (e.g. cardiac, blood cells,immune, brain and other tissues of the nervous system, and endothelium,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine; synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:137 as residues: Glu-72 to Gly-82, His-90 to Val-95, Gln-168 toLys-174, Val-202 to Ser-212.

[0099] The tissue distribution in endothelial cells combined with thehomology to calcium-activated potassium channels indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of vascular disorders(hyper/hypotension, athesma, pulmonary edema, pneumonia, heart disease,restenosis, atherosclerosis, stoke, angina and thrombosis). Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:27 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1085 of SEQID NO:27, b is an integer of 15 to 1099, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:27, and wherethe b is greater than or equal to a+14.

[0100] Features of Protein Encoded by Gene No: 18

[0101] This gene is expressed primarily in smooth muscle andhematopoietic cells and to a lesser extent in brain (amygdala, corpuscolosum, hippocampus).

[0102] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,cardiovascular (hypertension, heart disease, athesma, pulmonary edema,restenosis, atherosclerosis, stoke, angina, thrombosis, and woundhealing), immune, or neurological disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the cardiovascular and neurological systems, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g. immune, smooth muscle,vascular, and brain and other tissue of the nervous system, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:138 as residues: Lys-43 to Ar-49, Tyr-58 to Glu-65.

[0103] The tissue distribution in smooth muscle indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of cadiovascular disorders(hypertension, heart disease, athesma, pulmonary edema, restenosis,atherosclerosis, stoke, angina, thrombosis, and wound healing).Expression in brain indicates a role in the treatment and diagnosis ofbehavioral or neurological disorders, such as depression, schizophrenia,Alzheimer's disease, mania, dementia, paranoia, and addictive behavior.Expression of this gene product in hematopietic cells suggests a role inthe regulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer (e.g. by boostingimmune responses). Since the gene is expressed in cells of lymphoidorigin, the natural gene product may be involved in immune functions.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues. Many polynucleotide sequences,such as EST sequences, are publicly available and accessible troughsequence databases. Some of these sequences are related to SEQ ID NO:28and may have been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 927 of SEQ ID NO:28, b is an integer of 15 to941, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:28, and where the b is greater than or equalto a+14.

[0104] Features of Protein Encoded by Gene No: 19

[0105] This gene is expressed primarily in T-cells (Jurkats, resting,activated, and anergic T-cells), endothelial cells, pineal gland, and toa lesser extent in a variety of other tissues and cell types. Preferredpolypeptide fragments comprise the amino acid sequence:EEAGAGRRCSHGGARPAOLGNECLCLGGDPDHTDTGSRSKQRINNWKESKHKVIMASASARGNQDKDAHFPPPSKQSLLFCPKSKLHIHRAEISK (SEQ ID NO:263);and/or SKQRINNWKESKHKVIMASASAR (SEQ ID NO:264). Also preferred are thepolynucleotide fragments encoding these polypeptides.

[0106] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to immunedisorders, such as, inflammation, immunodeficiencies, or cardiovasculardisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of these tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune, neurological and vascular systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., T-cells and other blood cells,endothelial cells, and pineal gland, and cancerous and wounded tissues)or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:139 as residues: Phe-71 toAg-76, Pro-82 to His-87, Glu-103 to Ala-111.

[0107] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for the diagnosisand treatment of immune disorders including: leukemias, lymphomas,auto-immune, immuno-suppressive (e.g. transplantation) andimmunodeficiencies (e.g. AIDS) and hematopoietic disorders. In addition,expression in the pineal gland might suggest a role in the diagnosis ofspecific brain tumors and treatment of neurological disorders.Endothelial cell expression might suggest a role in cadiovascular orrespiratory/pulmonary disorders or infections (athesma, pulmonary edema,pneumonia). Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:29 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 742 of SEQ ID NO:29, b is an integer of 15 to756, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:29, and where the b is greater than or equalto a+14.

[0108] Features of Protein Encoded by Gene No: 20

[0109] The gene encoding the disclosed cDNA is thought to reside onchromosome 15. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis form chromosome 15.

[0110] This gene is expressed primarily in brain and embryo and to alesser extent in leukocytes.

[0111] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but art not limited to,developmental, immune, and neurological disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous and immunesystems, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g., brain.immune, cancerous and wounded tissues) or bodily fluids (e.g, lymph,amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having, the disorder. Preferred epitopes include those comprising asequence shown in SEQ ID NO:140 as residues: Met-1 to Gly-8.

[0112] The tissue distribution in immune tissues indicates thatpolynucleotides and polypeptides corresponding, to this gene are usefulfor the treatment and diagnosis of immune disorders including,:leukemias, lymphomas, auto-immune, immuno-suppressive (e.g,.transplantation) and immunodeficiencies (e.g. AIDS) and hematopoleticdisorders. The expression in the brain—and in particular the fetalbrain—would suggest a possible role in the treatment and diagnosis ofdevelopmental and neurodegenerative diseases of the brain and nervoussystem (depression, schizophrenia, Alzheimer's disease, mania, dementia,paranoia, and addictive behavior). Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:30 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 2086 of SEQ ID NO:30, b is aninteger of 15 to 2100, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:30, and where the b is greaterthan or equal to a+14.

[0113] Features of Protein Encoded by Gene No: 21

[0114] The gene encoding the disclosed cDNA is thought to reside onchromosome 17. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 17.

[0115] This gene is expressed primarily in brain, kidney, lung, liver,spleen, and a variety of leukocytes (especially T-cells) and to a lesserextent in a variety of other tissues and cell types.

[0116] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,leukemias, lymphomas, autoimmune, immunosuppressive, andimmunodeficiencies, hematopoietic disorders, as well as renal disorders,and neoplasms. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of therenal, pulmonary, immune, and central nervous systems, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., brain and other tissueof the nervous system, renal, pulmonary tissue, liver, spleen, and bloodcells, and cancerous and wounded tissues) or bodily fluids (e.g., lymph,bile, pulmonary surfactant or sputum, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0117] The tissue distribution in immune tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of renal conditions, such as acute renalfailure, kidney fibrosis, and kidney tubule regeneration. The expressionin leukocytes and other immune tissues indicates a role in immunedisorders including: leukemias, lymphomas, auto-immune,immuno-suppressive (e.g. transplantation) and immunodeficiencies (e.g.AIDS) and hematopoletic disorders. The expression in the brain—and inparticular the fetal brain—indicates a possible role in the treatmentand diagnosis of developmental and neurodegenerative diseases of thebrain and nervous system (depression, schizophrenia, Alzheimer'sdisease, mania, dementia, paranoia, and addictive behavior). Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:31 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1434 of SEQED NO:31, b is an integer of 15 to 1448, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:31, and wherethe b is greater than or equal to a+14.

[0118] Features of Protein Encoded by Gene No: 22

[0119] The gene encoding the disclosed cDNA is thought to reside onchromosome 19. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 19.

[0120] This gene is expressed primarily in skin (fetal epithelium,keratinocytes and skin).

[0121] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, skincancers (e.g, melanomas), eczema, psoriasis or other disorders of theintegumentary system. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of these tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theskin, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,keratinocytes, epithehium, integumentary, endothelial and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:142 as residues:Pro-28 to Glu-35, Ser-39 to Phe-44, Ala-94 to Gln-99.

[0122] The tissue distribution in integumentary tissue, suggests thatthe protein product of this clone would be useful for the treatment,diagnosis, and/or prevention of various skin disorders includingcongenital disorders (i.e. nevi, moles, freckles, Mongolian spots,hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses,Bowen's disease, basal cell carcinoma, squamous cell carcinoma,malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi'ssarcoma), injuries and inflammation of the skin (i.e. wounds, rashes,prickly heat disorder, psoriasis, dermatitis), atherosclerosis,uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupuserythematosus, vitiligo, dermatomyositis, morphea, scleroderma,pemphigoid, and pemphigus), keloids, striae, erythema, petechiae,purpura, and xanthelasma. Moreover, such disorders may predisposeincreased susceptibility to viral and bacterial infections of the skin(i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpeszoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot,and ringworm). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:32 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 442 of SEQ ID NO:32, b is an integer of 15 to456, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:32, and where the b is greater than or equalto a+14.

[0123] Features of Protein Encoded by Gene No: 23

[0124] This gene maps chromosome 11. Another group recently isolatedthis same gene, associating the sequence to the region thought to harborthe gene involved in Multiple Endocrine Neoplasia Type 1, or MEN 1. (SeeAccession No. 2529721 and Genome Res. 7(7), 725-735 (1997), incorporatedherein by reference in its entirety.) Preferred polypeptide fragmentscomprise the amino acid sequence: LFHWVACLEPRA AQLPRNTAXAGYQCPSCNGPS(SEQ ID NO:265).

[0125] This gene is expressed primarily in epididymus, pineal land,T-cells, as well as fetal epithelium, lung and kidney.

[0126] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immune,metabolic mediated disorders, reproductive, endocrine, and MEN.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immune,renal, neurological and pulmonary systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, epididymus and otherreproductive tissue, pineal gland, T-cells and other blood cells,epithelium, lung, and kidney, and cancerous and wounded tissues) orbodily fluids (e.g., seminal fluid, lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0127] The tissue distribution in fetal tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of developmental deficiencies orabnormalities as well as a host of different disorders which arise as aresult of conditions in the indicated tissues or cell types. An area ofparticular interest is in the treatment and diagnosis of immunedisorders including: leukemias, lymphomas, auto-immune,immuno-suppressive (e.g. transplantation) and immunodeficiencies (e.g.AIDS) and hematopoietic disorders. The expression in the brain, and inparticular the fetal brain, would suggest a possible role in thetreatment and diagnosis of developmental and neurodegenerative diseasesof the brain and nervous system (depression, schizophrenia, Alzheimer'sdisease, mania, dementia, paranoia, and addictive behavior).Respiratory/pulmonary disorders, such as athesma, pulmonary edema arealso potential therapeutic areas, as well as renal conditions such asacute renal failure, kidney fibrosis and kidney tubule regeneration.Moreover, this gene can be used in the treatment and/or detection of MENI. Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:33 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1312 of SEQID NO:33, b is an integer of 15 to 1326, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:33, and wherethe b is greater than or equal to a+14.

[0128] Features of Protein Encoded by Gene No: 24

[0129] This gene is expressed primarily in fetal spleen.

[0130] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited todevelopmental, leukemia, lymphoma, AIDS, hematopoietic disorders.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immune andhematopoietic systems, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g. immune, spleen, developmental, hepatic, hematopoietic, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, amnioticfluid, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0131] The tissue distribution in fetal spleen indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of immune disorders including:leukemias, lymphomas, auto-immune, immune-suppressive (e.g.transplantation) and immunodeficiencies (e.g. AIDS) and hematopoieticdisorders. Expression of this gene product in fetal spleen suggests arole in the regulation of the proliferation; survival; differentiation;and/or activation of potentially all hematopoietic cell lineages,including, blood stem cells. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:34 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 696 of SEQID NO:34, b is an integer of 15 to 710, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:34, and wherethe b is greater than or equal to a+14.

[0132] Features of Protein Encoded by Gene No: 25

[0133] A closely related homolog of this gene was recently cloned byanother group, calling the gene CDO, an oncogene-, serum-, andanchorae-regulated member of the Igifibronectin type III repeat family.(See Accession No. 2406628, and J. Cell Biol. 138(1): 203-213 (1997),herein incorporated by reference in its entirety.) Preferred polypeptidefragments comprise the amino acid sequence: FYIYYRPTDSDNDSDYKKDMVEGDKYWHSISKLQPETSYDIKMIQCFNEGGESEFSNVMICETKARKSSGQPGRLPPPTLAPPQPPLPETIEPPVGTGAMVARSSDLPYLIVGVVLGSIVLIIVTFIPFCLWRAWSKQKHTTDLGFPRSALPPSCPYTMVPLGOLPGHQAVDSPTSVASVD GPVLM (SEQ IDNO:266); or YIYYRPTDSDNDSDYKKDMVEODKYVHSISHLQPETSYDIKMQCFNEGGESEFSNVMCETKARKS (SEQ ID NO:267).

[0134] This gene is expressed primarily in fetal lung and kidney, humanembryo and osteoclastoma stromal cells and to a lesser extent in avariety of other tissues and cell types.

[0135] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,developmental disorders and cancers, as well as pulmonary and renaldisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of therespiratory/pulmonary, skeletal and renal systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., lung, kidney, embryonic tissue,and bone cells, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:145 as residues: Thr-5 toPro-18, Ala-76 to Thr-84.

[0136] The tissue distribution in fetal tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection and treatment of osteoporosis, fractures,osteosarcoma, ossification, and osteonecrosis, as well asrespiratory/pulmonary disorders, such as athesma, pulmonary edema, andrenal conditions such as acute renal failure, kidney fibrosis and kidneytubule regeneration. Alternatively, this gene may function in a tumorsuppression capacity, and it may be down-regulated by tumor cells orproto-oncogenes. Expression of this gene may be important in theprevention of tumor growth or metastasis. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:35 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1174 of SEQID NO:35, b is an integer of 15 to 1188, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:35, and wherethe b is greater than or equal to a+14.

[0137] Features of Protein Encoded by Gene No: 26

[0138] This gene is homologous to the HIV envelope glycoprotein. (SeeAccession No. 2641463.) Preferred polypeptide fragments comprise theamino acid sequence: NVALLHRMPEPPKINTAKFNNNKRKNLSL (SEQ ID NO:268).

[0139] This gene is expressed primarily in pineal gland and skin, and toa lesser extent in lung.

[0140] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,neurological and behavior disorders; respiratory/pulmonary disorders,such as athesma, pulmonary edema; skin conditions such as eczema,psoriasis, acne and skin cancer, as well as AIDS. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous and respiratorysystems, as well as skin and AIDS, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., blood cells, pineal gland,integumentary, endocrine, epidermis, and pulmonary tissue, and cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid or spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:146 as residues: Gln-15 to Gln-20.

[0141] The tissue distribution in integumentary tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of conditions which affect the abovetissues, such as skin cancer, eczema, psoriasis, acne, athesma,pulmonary edema, neuro-degenerative or developmental disorders such asAlzheimer's, depression, schizophrenia, dementia, and AIDS. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:36 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 942 of SEQID NO:36, b is an integer of 15 to 956, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:36, and wherethe b is greater than or equal to a+14.

[0142] Features of Protein Encoded by Gene No: 27

[0143] Preferred polypeptide encoded by this gene comprise the followingamino acid sequence: NTNQREALQYAKNFQPFALNHQKDIQVLMGSLVYLRQGIENSPYVHLLDANQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALINIKAVIEQRQCTGVWNQKDELPIEVDLOKKCWYYHSIFACPILRQQTTDNNPPMKLVCGHIISRDALNKMFNGSKLKCPYCMEQSPGDAKQIFF (SEQ ID NO:269). Polynucleotides encodingsuch polypeptides are also provided as are complementary polynucleotidesthereto. The gene encoding the disclosed cDNA is thought to reside onchromosome 2. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 2. Contact ofcells with supernatant expressing the product of this gene increases thepermeability of the plasma membranes of both astrocytes and monocytes tocalcium. Thus, it is likely that the product of this gene is involved insignal transduction pathway(s) which are initiated when the productbinds a receptor(s) on the surface of both astrocytes and monocytes.Thus, polynucleotides have uses which include, but are not limited to,activating astrocytes and monocytes.

[0144] This gene is expressed primarily in liver (adult and fetal) andspleen tissue, and to a lesser extent in placenta, T helper cells,kidney tumor, ovarian tumor, melanocytes and fetal heart.

[0145] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immuneand developmental diseases and disorders and liver diseases such asliver cancer. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune, circulatory and hematopoietic systems, expression of this geneat significantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., liver, spleen, placenta, bloodcells, developmental, kidney, ovary and other reproductive tissue,melanocytes, and heart, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, amniotic fluid, bile, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0146] The tissue distribution in immune cells indicates that theprotein products of this gene are useful for study, diagnosis andtreatment of growth, hematopoietic and immune system disordersparticularly related to the liver. Expression of this gene product inhematopoletic cells suggests a role in the regulation of theproliferation; survival; differentiation; and/or activation ofpotentially all hematopoletic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, leukemia,rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, andpsoriasis. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:37 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1589 of SEQ ID NO:37, b is an integer of 15 to1603, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:37, and where the b is greater than or equalto a+14.

[0147] Features of Protein Encoded by Gene No: 28

[0148] The translation product of this gene shares sequence homologywith prostaglandin transporter which is thought to be important inmetabolic and endocrine disorders. See, for example, GastroenterologyOct: 109(4):1274-1282 (1995). Preferred polypeptides encoded by thisgene comprise the following amino acid sequence:SYLSACFAGCNSTNLTGCACLTTYPAENATVVPGKCPSPGCQEAFLTFLCVIMCI CSLIGAMARHP (SEQID NO:270); and/or PSVIILIRTVSPELKSYALGVLFLLRLLGFIPPPLIFGAGIDSTCLFWSTFCGEQGACVLYDNVVRYLYVSIALIALKSFAFI (SEQ ID NO:271).

[0149] This gene is expressed primarily in hematopoietic and braintissues.

[0150] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,metabolic, immune and endocrine diseases and disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the metabolic, immune and endocrinesystems, expression of tis gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, endocrine tissue, hematopoietic tissue, and brain and othertissue of the nervous system, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0151] The tissue distribution in hematopoietic cells combined with thehomology to a prostaglandin (and anion) transporter indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor study, diagnosis and treatment of endocrine, metabolic, immune andkidney disorders. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:38 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of abb, where a isany integer between 1 to 1075 of SEQ ID NO:38, b is an integer of 15 to1089, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:38, and where the b is greater than or equalto a+14.

[0152] Features of Protein Encoded by Gene No: 29

[0153] This gene is expressed primarily in early stage human lung.

[0154] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, growthand respiratory disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe developmental and respiratory systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., pulmonary tissue, developmental,and cancerous and wounded tissues) or bodily fluids (e.g., amnioticfluid, lymph, pulmonary, surfactant or sputum, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:149 as residues:Val-50 to Trp-55.

[0155] The tissue distribution in fetal lung indicates that the proteinproducts of this gene are useful for study, diagnosis and treatment ofrespiratory and growth diseases and disorders. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:39 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 615 of SEQID NO:39, b is an integer of 15 to 629, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:39, and wherethe b is greater than or equal to a+14.

[0156] Features of Protein Encoded by Gene No: 30

[0157] The translation product of this gene shares sequence homologywith human DNA helicase which is thought to be important in accurate andcomplete DNA replication in creation of new cells. Preferredpolypeptides encoded by this gene comprise the following amino acidsequence: QSLFTRFVRVGVPTVDLDAQGRARASLCXXYNWRYKNLGNLPHVQLLPEFSTANAGLLYDFQLINVEDFQGVGESEPNPYFYQNLGEAEYVVALFMYMCLLGYPADKISILTTYNGQKHLIRDIINRRCGNNPLIGRPNKVTTDRPQGQQNDYILLSLVRTRAVGHLRDVRRLVVAMSRAR (SEQ ID NO:272);and/or LVKEAKILAMTCTHAALKRHDLVKLGFKYDNILMEEAAQILETETFLPLLLQNPQDGFSRLKRWIMIGDHHQLPPVI (SEQ ID NO:273). The geneencoding the disclosed cDNA is thought to reside on chromosome 15.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 15.

[0158] This gene is expressed primarily in testes tumor and to a lesserextend in adrenal gland tumor and placenta.

[0159] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,reproductive disorders, cancers and endocrine/growth disorders.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the endocrine,developmental, and reproductive systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g, testes and other reproductivetissue, adrenal gland, and placenta, and cancerous and wounded tissues)or bodily fluids (e.g., seminal fluid, serum, plasma, urine, synovialfluid, or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0160] The tissue distribution in testes combined with the homology to aDNA helicase indicates that the protein products of this gene are usefulfor study, treatment, and diagnosis of many cancer types, includingtesticular cancer, as well as disorders involving endocrine function andnormal growth and development. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:40 and may have been publicly available prior to conception of thepresent intention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1950 of SEQ ID NO:40, b is aninteger of 15 to 1964, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:40, and where the b is greaterthan or equal to a+14.

[0161] Features of Protein Encoded by Gene No: 31

[0162] The translation product of this gene shares sequence homologywith BID-apoptotic death gene (mouse), Genbank accession no. PIDg1669514, which is thought to be important in programmed cell death.

[0163] This gene is expressed primarily in jurtat membrane boundpolysomes and activated neutrophils and to a lesser extent inendothelial cells and human cerebellum.

[0164] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, cancersand other proliferative disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. immune, blood cells, hematopoletic,endothelium, and brain and other tissue of the nervous system, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:151 as residues: Glu-4 to Leu-11, Cys-28 to Arg-35, Gln-50 to His-66,Glu-73 to Gln-79, Gly-94 to Ser-100, Arg-114 to Asp-126, Pro-139 toLys-146.

[0165] The tissue distribution in immune cells combined with thehomology to the BID-apoptotic death gene indicates that the proteinproducts of this gene are useful for study of cell death, and treatmentand diagnosis of proliferative disorders and cancers.Apoptosis—programmed cell death—is a physiological mechanism involved inthe deletion of peripheral T lymphocytes of the immune system, and itsdysregulation can lead to a number of different pathogenic processes.Diseases associated with increased cell survival, or the inhibition ofapoptosis, include cancers (such as follicular lymphomas, carcinomaswith p53 mutations, and hormone-dependent tumors, such as breast cancer,prostrate cancer. Kaposiis sarcoma and ovarian cancer); autoimmunedisorders (such as systemic lupus erythematosus and immune-relatedglomerulonephritis rheumatoid arthritis) and viral infections (such asherpes viruses, pox viruses and adenoviruses), inflammation; graft vs.host disease, acute graft rejection, and chronic graft rejection.Diseases associated with increased apoptosis include AIDS;neurodegenerative disorders (such as Alzheimer's disease, Parkinson'sdisease, Amyotrophic lateral sclerosis, Retinitis pigmentosa, Cerebellardegeneration); myelodysplastic syndromes (such as aplastic anemia),ischemic injury (such as that caused by myocardial infarction, strokeand reperfusion injury), toxin-induced liver disease (such as thatcaused by alcohol), septic shock, cachexia and anorexia. Thus, theinvention provides a method of enhancing apoptosis in an individual bytreating the individual with a polypeptide encoded by this gene.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:41 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 1508 of SEQ ID NO:41, b is an integer of 15 to 1522, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:41, and where the b is greater than or equal to a+14.

[0166] Features of Protein Encoded by Gene No: 32

[0167] The translation product of this gene shares sequence homologywith human fructose transporter which is thought to be important innormal metabolic function and activity.

[0168] This gene is expressed primarily in T-cell lymphoma.

[0169] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, leukemiaand other cancers, and metabolic disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hematopoietic, lymph and metabolic systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g. immune, brain,T-cells and other blood cells, metabolic tissues, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:152 as residues:Pro-29 to Gly-48, Ser-54 to Pro-61.

[0170] The tissue distribution in T-cell lymphoma indicates that theprotein products of this gene are useful for study of mechanisms leadingto cancer, treatment and diagnosis of cancerous and pre-cancerousconditions; as well as the study and treatment of various metabolicdiseases and disorders. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues. Many polynucleotide sequences,such as EST sequences, are publicly available and accessible throughsequence databases. Some of these sequences are related to SEQ ID NO:42and may have been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of cub, where a isany integer between 1 to 861 of SEQ ID NO:42, b is an integer of 15 to875, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:42, and where the b is greater than or equalto a+14.

[0171] Features of Protein Encoded by Gene No: 33

[0172] This gene is expressed primarily in human meningima and placentaltissues.

[0173] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,inflammation and other disorders of the CNS. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the CNS and immune systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. immune, meningima, developmental,proliferating, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:153 as residues: Asn-23 toPro-31.

[0174] The tissue distribution in neural tissue indicates that theprotein products of this gene are useful for study, diagnosis andtreatment of disorders of the CNS and inflammatory responses. Protein,as well as, antibodies directed against the protein may show utility asa tumor marker and/or immunotherapy targets for the above listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:43 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 829 of SEQID NO:43, b is an integer of 15 to 843, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:43, and wherethe b is greater than or equal to a+14.

[0175] Features of Protein Encoded by Gene No: 34

[0176] This gene is expressed primarily in activated monocytes and woundhealing tissues and to a lesser extent in fetal epithelium.

[0177] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immuneand inflammatory disorders and wound healing and tissue repairdysfunctions. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune, epithelial and gastrointestinal systems, and healing wounds,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g. immune,keratinocytes, monocytes, integumentary, developmental, and other bloodcells, and epithelium, and cancerous and wounded tissues) or bodilyfluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:154 as residues:Ala-28 to Ala-33, Gly-35 to Glu-45.

[0178] The tissue distribution in immune cells indicates that theprotein products of this gene are useful for diagnosis, study andtreatment of immune and inflammatory disorders and wound healingdysfunctions. Expression of this gene product in immune cells suggests arole in the regulation of the proliferation; survival; differentiation;and/or activation of potentially all hematopoietic cell lineages,including blood stem cells. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid ohgin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible though sequence databases. Some of thesesequences are related to SEQ ID NO:44 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 475 of SEQID NO:44, b is an integer of 15 to 489, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:44, and wherethe b is greater than or equal to a+14.

[0179] Features of Protein Encoded by Gene No: 35

[0180] This gene is expressed primarily in human osteosarcoma andprostate cancer.

[0181] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, skeletaland neoplastic conditions such as bone and prostate cancer. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune and skeletal systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., immune, bone,prostate, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:155 as residues: Ser-14 to Gly-22, Leu-37 to Gln-43.

[0182] The tissue distribution in skeletal cells indicates that theprotein products of this gene are useful for diagnosis and treatment ofskeletal disorders and cancer. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:45 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 520 of SEQ ID NO:45, b is aninteger of 15 to 534, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:45, and where the b is greaterthan or equal to a+14.

[0183] Features of Protein Encoded by Gene No: 36

[0184] This gene encodes a protein which is highly homologous to aprotein called congenital heart disease protein 5, presumably implicatedin congenital heart disease (see Genbank PID g2810996).

[0185] This gene is expressed primarily in Hodgkin's lymphoma,erythroleukemia cells, and TNF activated synovial fibroblasts, to alesser extent in ovarian cancer, cerebellum, spleen, fetal liver andplacenta and finally to a lesser extent in various other mesenchymaltissues.

[0186] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, cancer,immune, hematopoletic and cardiovascular disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune, hematopoletic andcardiovascular systems, expression of his gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., heart and other cardiovascular tissue, immune, lymphoidtissue, blood cells, bone marrow, ovary and other reproductive tissue,brain and other tissue of the nervous system, spleen, liver, andmesenchymal tissue, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, bile, amniotic fluid, serum, plasma, urine, synovial fluidor spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:156 as residues:Lys-41 to Met-49, Gln-54 to Glu-59, Glu-76 to Thr-88.

[0187] The homology of this gene and translation product to congenitalheart disease protein 5 indicates a role for this protein in thediagnosis, prognosis and/or treatment of heart disease or othercardiovascular related disorders. In addition, predominant expression incells associated with the immune and hematopoetic system indicates arole for this protein in the treatment, diagnosis and/or prognosis ofimmune and autoimmune diseases, such as lupus, transplant rejection,allergic reactions, arthritis, asthma, immunodeficiency diseases,leukemia, AIDS, thymus disorders such as Graves Disease, lymphocyticthyroiditis, hypert, hyroidism and hypothyroidism, graft versus hostreaction, graft versus host disease, transplant rejection, myelogenousleukemia, bone marrow fibrosis, and myeloproliferative disease. Theprotein could also be used to enhance or protect proliferation,differentiation and functional activation of hematopoietic progenitorcells such as bone marrow cells, which could be useful for cancerpatients undergoing chemotherapy or patients undergoing bone marrowtransplantation. The protein may also be useful to increase theproliferation of peripheral blood leukocytes, which could be useful inthe combat of a range of hematopoietic disorders includingimmunodeficiency diseases, leukemia, and septicemia. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:46 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1360 of SEQID NO:46, b is an integer of 15 to 1374, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:46, and wherethe b is greater than or equal to a+14.

[0188] Features of Protein Encoded by Gene No: 37

[0189] This gene is expressed primarily in ovarian cancer.

[0190] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,urogenital neoplasias, reproductive, or endocrine disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the reproductive system, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., ovary and otherreproductive tissue, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder. Preferred epitopes include those comprising asequence shown in SEQ ID NO:157 as residues: Asn-22 to Asn-27.

[0191] The tissue distribution in ovarian tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor study, diagnosis and treatment of ovarian and other tumors. Protein,as well as, antibodies directed against the protein may show utility asa tumor marker and/or immunotherapy targets for the above listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:47 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 582 of SEQID NO:47, b is an integer of 15 to 596, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:47, and wherethe b is greater than or equal to a+14.

[0192] Features of Protein Encoded by Gene No: 38

[0193] The translation product of this gene shares sequence homologywith zinc finger proteins, which are small DNA-binding molecules notedfor their occurrence in a large number of eukaryotic transcriptionfactors.

[0194] This gene is expressed primarily in fetal, cancer, andendothelial lines.

[0195] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immuneand growth disorders. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thecardiovascular system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g. immune, fetal tissue, and endothelial cells, and cancerousand wounded tissues) or bodily fluids (e.g., lymph, bile, amnioticfluid, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0196] The tissue distribution in fetal tissue indicates that theprotein products of this gene are useful for study, diagnosis andtreatment of immune and developmental conditions and cancer. Thehomology to zinc finger proteins suggests that this protein may play arole in the transcriptional regulation of certain cancer genes. Protein,as well as, antibodies directed against the protein may show utility asa tissue-specific marker and/or immunotherapy target for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences ire related to SEQ ID NO:48 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 837 of SEQ ID NO:48, b is an integer of 15 to 851, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:48, and where the b is greater than or equal to a+14.

[0197] Features of Protein Encoded by Gene No: 39

[0198] This gene is expressed primarily in fetal, infant, and adultbrain and to a lesser extent in other brain and endocrine organs andblastomas.

[0199] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, braintumors and neurodegenerative conditions, in addition to developmentaldisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thenervous and endocrine systems, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., brain and other tissue of the nervous system,endocrine tissue, and cancerous and wounded tissues) or bodily fluids(e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0200] The tissue distribution in neural tissue indicates that theprotein products of this gene are useful for the study, diagnosis andtreatment of brain cancer and other neurological disorders such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsivedisorder, panic disorder, learning disabilities, ALS, psychoses, autism,and altered bahaviors, including disorders in feeding, sleep patterns,balance, and preception. In addition, the gene or gene product may alsoplay a role in the treatment and/or detection of developmental disordersassociated with the developing embryo, sexually-linked disorders, ordisorders of the cardiovascular system. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:49 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 2006 of SEQ ID NO:49, b is aninteger of 15 to 2020, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:49, and where the b is greaterthan or equal to a+14.

[0201] Features of Protein Encoded by Gene No: 40

[0202] The translation product of this gene shares sequence homologywith vesicular glycoproteins and lectins. Preferred polypeptides encodedby this gene comprise the following amino acid sequence:DTYPNEEKQQERVFPXXSAMVNNGLSYDHERDGRPTELGGCXAIVRNLHYDTFLVIRYVKRHLTIMMDIDGKHEWRDCIEVPGVRLPRGYYFGTSSITGDLSDNHDVISLKLFELTVERTPEEE (SEQ ID NO:274); and/orLKREHSLSKPYQGVGTGSSSLWNLMGNAMVMTQYIRLTPDMQSKQGALWNRVPCFLRDNELQVHFKIHGQGKKNLHGDGLAIWYT (SEQ ID NO:275). The geneencoding the disclosed cDNA is thought to reside on chromosome 2.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 2. When tested against U937myeloid cell lines and Jurkat T-cell lines, supernatants removed fromcells containing this gene activated the GAS pathway. Thus, it is likelythat this gene activates myeloid cells and T-cells through the Jaks-STATsignal transduction pathway. The Gamma Activating Sequence (GAS) is apromoter element found upstream of many genes which are involved in theJaks-STAT pathway. The Jaks-STAT pathway is a large, signal transductionpathway involved in the differentiation and proliferation of cells.Therefore, activation of the Jaks-STAT pathway, reflected by the bindingof the GAS element, can be used to indicate proteins involved in theproliferation and differentiation of cells. When tested against sensoryneuron cell lines, supernatants removed from cells containing this geneactivated the EGR1 pathway. Thus, it is likely that this gene activatessensory neuron cells through a signal transduction pathway induced bythe EGR1 promoter. The Early Growth Response Gene 1 (EGR1) is a separatesignal transduction pathway in which the EGR1 promoter induces varioustissues and cell types upon activation, leading the cells to undergodifferentiation and proliferation.

[0203] This gene is expressed primarily in infant brain and to a lesserextent in various normal and transformed neural, endocrine, and immuneorgans.

[0204] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,neurological and neurodevelopmental conditions. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the nervous and hormonal systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues (e.g. brain and other tissue of the nervous system,endocrine tissue, and tissue and cells of the immune system,developmental disorders, and cancerous and wounded tissues) or bodilyfluids (e.g., amniotic fluid, lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:160 as residues:Pro-64 to Gly-71, Gly-94 to Leu100, Thr-110 to Pro-116, Thr-135 toArg-145, Glu-164 to Glu-171, Asp-204 to Asp-21 1, Arg-253 to His-261,Asn-312 to Tyr-323.

[0205] The tissue distribution in neural tissue indicates that theprotein products of this gene are useful for the study, diagnosis andtreatment of mental retardation and other neurological disorders andneoplasias. The activity of this gene seen in various biological assaysindicates that this gene is involved in a number of signal transductionassays, which further suggests that this gene could be important in cellproliferation and differentiation. Protein, as well as, antibodiesdirected against the protain may show utility as a tissue-specificmarker and/or immunotherapy target for the above-listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:50 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 2418 of SEQID NO:50, b is an integer of 15 to 2432. where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:50, and wherethe b is greater than or equal to a+14.

[0206] Features of Protein Encoded by Gene No: 41

[0207] This gene displays homology to the glycosyltransferase family,which catalyze the addition of sialic acids to carbohydrate groups whichare present on glycoproteins and glycolipids.

[0208] This gene is expressed primarily in smooth muscle and to a lesserextent in pineal gland, fetal liver, and infant brain.

[0209] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,gastrointestinal injury, inflammatory and neurodegenerative conditions,endocrine, hematopoletic, hepatic or developmental disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune and nervous systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., smoothmuscle, pineal gland, liver, and brain and other tissue of the nervoussystem, and cancerous and wounded tissues) or bodily fluids (e.g.,amniotic fluid, lymph, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:161 as residues: Ser-12 toTrp-21, Arg-24 to Pro-32, Asp-73 to Lys-82, Lys-90 to Ala-97.

[0210] The tissue distribution in neural and fecal tissue indicates thatthe protein products of this gene are useful for the study, diagnosisand treatment of neurodegenerative and growth disorders andgastrointestinal repair. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:51 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 2326 of SEQ ID NO:51, b is aninteger of 15 to 2340, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:51, and where the b is greaterthan or equal to a+14.

[0211] Features of Protein Encoded by Gene No: 42

[0212] The translation product of this gene shares sequence similaritywith metallothionein polypeptides. See, for example, Proc. Natl. Acad.Sci. U S A 1992 July 15:89 (14):6333-6337. Metallothioneins are believedto inhibit neuronal survival among other biological functions. Based onthe sequence similarity (especially the conserved cysteine motifscharacteristic of the metallothionein family) the translation product ofthis gene is expected to share certain biological activities with othermembers of the metallothionein polypeptide family. Preferredpolypeptides encoded by this gene comprise the following amino acidsequence: POTLQCSALHHDPGCANCSRFCRD CSPPACQC (SEQ ID NO:276).

[0213] This gene is expressed exclusively in placenta and fetal liver,and to a lesser extent in osteoblast and bone marrow cells.

[0214] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,hematopoletic and immune disorders and hepatic or skeletal systemconditions. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thereproductive and immune systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, placenta, liver, brain andother tissue of the nervous system, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, amniotic fluid, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0215] The tissue distribution in immune cells and homology tometallothionien indicates that the protein products of this gene areuseful for diagnosis and treatment of immune and hematopoietic systemdisorders and neurological diseases, especially in fetal development.Expression of this gene product in hematopoietic cells suggests a rolein the regulation of the proliferation; survival; differentiation;and/or activation of potentially all hematopoietic cell lineages,including blood stem cells. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:52 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 587 of SEQID NO:52, b is an integer of 15 to 601, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:52, and wherethe b is greater than or equal to a+14.

[0216] Features of Protein Encoded by Gene No: 43

[0217] Preferred polypeptides encoded by this gene comprise thefollowing amino acid sequence: FLYDVLMXXEAVNIRTHQIQLPDPEFPS (SEQ IDNO:277).

[0218] This gene is expressed primarily in T-cells and synovial tissue.

[0219] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immunesystem disorders. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain issues or cell types (e.g.,synovial tissue, and T-cells and other blood cells, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0220] The tissue distribution in T-cells indicates that the proteinproducts of this gene, are useful for treatment and diagnosis ofdisorders of the immune system. Expression of this gene product inimmune cells suggests a role in the regulation of the proliferation;survival; differentiation; and/or activation of potentially allhematopoietic cell lineages, including blood stem cells. This geneproduct may be involved in the regulation of cytokine production,antigen presentation, or other processes that may also suggest ausefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, leukemia,rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, andpsoriasis. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:53 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 345 of SEQ ID NO:53, b is an integer of 15 to359, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:53, and where the b is greater than or equalto a+14.

[0221] Features of Protein Encoded by Gene No: 44

[0222] The translation product of this gene shares sequence similaritywith several methyltransferases (e.g., see Genbank gil1065505) whichsuggests this protein would be important in normal developmental andcellular processes.

[0223] This gene is expressed primarily in ovary, thymus, infant adrenalgland, tissues of the nervous system and the hematopoietic tissue, andto a lesser extent in adipose tissue and other tissues.

[0224] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,disorders of the reproductive system, the endocrine-system, thehematopoletic system and the CNS. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune, endocrine, CNS and reproductive system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., ovary and other reproductivetissue, thymus, adrenal gland, brain and other tissue of the nervoussystem, hematopoietic tissue, and adipose tissue, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:164 as residues:Ser-3 to Gly-12, Asp-19 to Arg-31, Tyr-70 to Tyr-77, Asn-130 to Lys-140,Pro-165 to Gln-170, Pro-192 to Lys-199, Leu-216 to Glu-227, Glu-254 toPhe-281.

[0225] The tissue distribution in hematopoietic cells and homology tomethyltransferase indicates that the protein products of this gene areuseful for diagnosis and treatment of disorders of the CNS, thehematopoietic system and reproductive organs and tissues. For example,the abundant expression in the ovary may indicate that the gene productcan be used as a hormone with either systemic or reproductive functions;as growth factors for germ cell maintenance and in vitro culture; as afertility control agent; remedy for sexual dysfunction or sexdevelopment disorders; diagnostics/treatment for ovarian tumors, such asserous adenocarcinoma, dysgerminoma, embryonal carcinoma,choriocarcinoma, teratoma, etc; The expression in thymus may indicateits utility in T-cell development and thus its applications in immunerelated medical conditions, such as infection, allergy, immunedeficiency, tissue/organ transplantation, etc. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:54 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1127 of SEQID NO:54, b is an integer of 15 to 1141, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:54, and wherethe b is greater than or equal to a+14.

[0226] Features of Protein Encoded by Gene No: 45

[0227] The translation product of this gene shares sequence homologywith cytochrome C oxidase which is thought to be important in themetabolic function of cells. This gene has now recently been publishedas estrogen response gene. See Genbank accession no. AB007618 and Mol.Cell. Biol. 18 (1), 442-449 (1998). See also J Immunol. March 1:154(5):2384-2392 (1995), where the mouse homologue was published and implicatedin silicosis. In specific embodiments, polypeptides of the inventioncomprise the following amino acid sequence: PADXKPVSTEAPPffFATPTKLTSDSTYDYAGKNKPELQKFFQKADGVPVYLKRGLPDQMLYRTTMALTVGGTIYCLIAL YMASQPKNK (SEQ IDNO:278) or SFSGAVALAKDAGSRTLGVMYYKFSGFTQKLAGAWASEAYSPQLXSLWFPQKHHLSYLPHQLN (SEQ ID NO:279). Polynucleotidesencoding these polypeptides are also encompassed by the invention. Thegene encoding the disclosed cDNA is believed to reside on chromosome 2.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 2.

[0228] This gene is expressed primarily in adipose tissue, kidney andfetal brain and to a lesser extent in other tissues and organs.

[0229] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,metabolic diseases involving especially adipose tissue, brain andkidney. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theCNS and vascular system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., adipose tissue, kidney, brain and other tissue of thenervous system, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid orspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:165 as residues: Thr-8 toSer-13, Ser-29 to Ala-34, Pro-64 to Lys-77.

[0230] The tissue distribution and homology to cytochrome C oxidase,estrogen response gene product and silicosis related gene productindicates that the protein products of this gene are useful fordiagnosis and treatment of metabolic disorders in the CNS, adiposetissue and kidney, particularly silicosis. Expression within fetalsuggests that this protein may play a role in the regulation of cellulardivision, and may show utility in the diagnosis and treatment of cancerand other proliferative disorders. Similarly, embryonic development alsoinvolves decisions involving cell differentiation and/or apoptosis inpattern formation. Thus this protein may also be involved in apoptosisor tissue differentiation and could again be useful in cancer therapy.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:55 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 1546 of SEQ ID NO:55, b is an integer of 15 to 1560, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:55, and where the b is greater than or equal to a+14.

[0231] Features of Protein Encoded by Gene No: 46

[0232] The translation product of this gene shares sequence homologywith reticulocalbin. See, for example, J. Biochem. 117 (5), 1113-1119(1995). Based on the sequence similarity, the translation product ofthis gene is expected to share certain biological activities withreticulocalbin, e.g., Ca++ binding activities. This gene product issometimes hereinafter referred to as “Reticulocalbin-2”. When testedagainst Jurkat T-cell lines, supernatants removed from cells containingthis gene activated the GAS pathway. Thus, it is likely that this geneactivates T-cells through the Jaks-STAT signal transduction pathway. TheGamma Activating Sequence (GAS) is a promoter element found upstream ofmany genes which are involved in the Jaks-STAT pathway. The Jaks-STATpathway is a large, signal transduction pathway involved in thedifferentiation and proliferation of cells. Therefore, activation of theJaks-STAT pathway, reflected by the binding of the GAS element, can beused to indicate proteins involved in the proliferation anddifferentiation of cells. When tested against K562 leukemia cell lines,supernatants removed from cells containing this gene activated the ISREpathway. Thus, it is likely that this gene activates leukemia cellsthrough a signal transduction pathway induced by the ISRE promoter. TheInterferon-Sensitive Responsive Element (ISRE) is a promoter elementfound upstream in many genes which are involved in the Jaks-STATpathway. The Jaks-STAT pathway is a large, signal transduction pathwayinvolved in the differentiation and proliferation of cells. Therefore,activation of the Jaks-STAT pathway, reflected by the binding of theISRE element, can be used to indicate proteins involved in theproliferation and differentiation of cells.

[0233] This gene is expressed primarily in breast, endothelial cells,synovial, heart and smooth muscle cells.

[0234] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, diseasesof the breast, vascular, skeletal/cardiac muscular system as well as theintegumentary system. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thebreast, vascular and skeleto-muscular system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., mammary tissue, endothelial cells,synovial tissue, heart and other cardiovascular tissue, smooth muscle,integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, breast milk, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:166 as residues: Gly-16 toArg-2, Ala-42 to Asn-50, Glu-66 to Gln-76, Arg-85 to Gly-94, Thr-108 toAsp-115, Trp-121 to Gly-130, Leu-137 to His-144, Glu-155 to Lys-161,Asp-175 to Ser-180, Glu-209 to Gly-217, Glu-232 to Glu-237, Thr-243 toAsp-261, Glu-87 to Arg-295.

[0235] The tissue distribution in smooth muscle cells indicates that theprotein products of this gene are useful for diagnosis and treatment ofdiseases of the vascular and skeletal/cardiac muscular system. Thehomology of the gene with reticulocalbin indicates its biologicalfunction in regulating calcium store, a particularly important functionin muscular cell types. The gene expression in the heart may indicateits utilities in diagnosis and remedy in heart failure, ischemic heartdiseases, cardiomyopathy, hypertension, arrhythmia, etc. The abundantexpression in the breast may indicate its applications in breastneoplasia and breast cancers, such as fibroadenoma, papillary carcinoma,ductal carcinoma, Paget's disease, medullary carcinoma, mucinouscarcinoma, tubular carcinoma, secretory carcinoma and apocrinecarcinoma; juvenile hypertrophy and gynecomastia, mastitis and abscess,duct ectasia, fat necrosis and fibrocystic diseases, etc. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:56 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1493 of SEQID NO:56, b is an integer of 15 to 1507, where both a and b correspondto the positions of-nucleotide residues shown in SEQ ID NO:56, and wherethe b is greater than or equal to a+14.

[0236] Features of Protein Encoded by Gene No: 47

[0237] The translation product of this gene shares weak sequencehomology with H+-transporting ATP synthase which is thought to beimportant in cell metabolism or signal transduction.

[0238] This gene is expressed only in testis.

[0239] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of sometypes of diseases and conditions. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe brain and hematopoietic tissues, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., testes and other reproductivetissue, and cancerous and wounded tissues) or bodily fluids (e.g. lymph,seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0240] Since only one out of about a million expressed sequence tags arefound in testes, it is reasonable to suggest that the expression of thisgene is selective for testes. Since some of the genes only expressed intestes are usually expressed in brain or in certain inducedhematopoletic cells/tissues, it is speculated that this gene will beexpressed in brain or hematopoietic cells/tissues and is useful fordiagnosis and treatment of disorders of these systems. Similarly, thesecreted protein can also be used to determine biological activity, toraise antibodies, as tissue markers, to isolate cognate ligands orreceptors, to identify agents that modulate their interactions and asnutritional supplements. It may also have a very wide range ofbiological activities. Typical of these are cytokine, cellproliferation/differentiation modulating activity or induction of othercytokine; immunostimulating/immunosuppressant activities (e.g. fortreating human immunodeficiency virus infection, cancer, autoimmunediseases and allergy); regulation of hematopoiesis (e.g. for treatinganaemia or as adjunct to chemotherapy); stimulation or growth of bone,cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds,stimulation of follicle stimulating hormone (for control of fertility);chemotactic and chemokinetic activities (e.g. for treating infections,tumors); hemostatic or thrombolytic activity (e.g. for treatinghaemophilia, cardiac infarction etc.); anti-inflammatory, activity (e.g.for treating septic shock, Crohn's disease); as antimicrobials; fortreating psoriasis or other hyperproliferative diseases; for regulationof metabolism, and behaviour. Also contemplated is the use of thecorresponding nucleic acid in gene therapy procedures. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed-tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:57 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 436 of SEQID NO:57, b is an integer of 15 to 450, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:57, and wherethe b is greater than or equal to a+14.

[0241] Features of Protein Encoded by Gene No: 48

[0242] The translation product of this gene shares sequence homologywith human polymeric immunoglobulin receptor (accession No.X73079) whichis thought to be important in antibody recognition and immune defenses.In one embodiment, polypeptides of the invention comprise the sequenceGWYWCG (SEQ ID NO:230). Polynucleotides encoding these polypeptides arealso encompassed by the invention. The gene encoding the disclosed cDNAis believed to reside on chromosome 1. Accordingly, polynucleotidesrelated to this invention are useful as a marker in linkage analysis forchromosome 1.

[0243] This gene is expressed primarily in placenta and to a lesserextent in corpus callosum and fetal liver and spleen.

[0244] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,disorders of the immune system, e.g. autoinune diseases andimmunodeficiency, in addition to developmental disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues and cell types (e.g., placenta, liver, and spleen,developmental tissues, and cancerous and wounded tissues) or bodilyfluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluidor spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferredepitopestinclude those comprising a sequence shown in SEQ ID NO. 168 asresidues: Tyr-37 to Cys-49, Gly-51 to Tyr-56, Lys-88 to Trp-93, Leu-130to Glu-136.

[0245] The tissue distribution in fetal liver and spleen combined withthe homology to human polymeric immunoglobulin receptor indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of immune disorders, e.g. autoimmunediseases and immunodeficiencies. Expression within fetal tissues andother cellular sources marked by proliferating cells suggests that thisprotein may play a role in the regulation of cellular division, and mayshow utility in the diagnosis and treatment of cancer and otherproliferative disorders. Similarly, embryonic development also involvesdecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:58 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1133 of SEQID NO:58, b is an integer of 15 to 1147, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:58, and wherethe b is greater than or equal to a+14.

[0246] Features of Protein Encoded by Gene No: 49

[0247] This gene is expressed in thymus.

[0248] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immunedisorders, such as inflammation or immunodeficiencies. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues (e.g, immune, hematopoietic, thymus and cancerous andwounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0249] The tissue distribution in thymus indicates that polynucleotidesand polypeptides corresponding to this gene are useful for diagnosis andtreatment of immune disorders, such as autoimmunity and immunodeficiencydisorders. Similarly, this gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immunodeficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, granulomatousdisease, inflammatory bowel disease, sepsis, acne, neutropenia,neutrophilia, psoriasis. hypersensitivities, such as T-cell mediatedcytotoxicity; immune reactions to transplanted organs and tissues, suchas host-versus-graft and graft-versus-host diseases, or autoimmunitydisorders, such as autoimmune infertility, lense tissue injury,demyelination, systemic lupus erythematosis, drug induced hemolyticanemia, rheumatoid arthritis, Sjogren's disease, scieroderma andtissues. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:59 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 763 of SEQ ID NO:59, b is an integer of 15 to777, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:59, and where the b is greater than or equalto a+14.

[0250] Features of Protein Encoded by Gene No: 50

[0251] Preferred polypeptide encoded by this gene comprise the followingamino acid sequence: MKVGARIRVKMSVNKAHPVVSTHWRWPAEWPQMFLHLAWEPRTEVKSRPLGLAGFIRQDSKTRKPLEQETIMSAADTALWPYGHGNREHQENELQKYLQYKDNIHLLDSGQSLGHTHTLQGSHNLTALNI (SEQ ID NO:281). Polynucleotidesencoding this polypeptide are also provided as are complementarypolynucleotides thereto.

[0252] This gene is expressed primarily in adrenal gland, pituitary, Thelper cells, and breast cells and to a lesser extent in a wide varietyof tissues.

[0253] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of thesome diseases and conditions. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune and endocrine systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., adrenal gland, pituitary, T-cellsand other blood cells, and mammary tissue, and cancerous and woundedtissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma,urine, synovial fluid or spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:170 as residues: Gln-39 to Ser-47, Arg-57 to Glu-67, Tyr-82 toGln-95.

[0254] The tissue distribution in immune tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of a wide range of disorders, such as immuneand endocrine disorders. Similarly, the secreted protein can also beused to determine biological activity, to raise antibodies, as tissuemarkers, to isolate cognate ligands or receptors, to identify accentsthat modulate their interactions and as nutritional supplements. It mayalso have a very wide range of biological activities. Typical of theseare cytokine, cell proliferation/differentiation modulating activity orinduction of other cytokines; immunostimulating/immunosuppressantactivities (e.g. for treating human immunodeficiency virus infection,cancer, autoimmune diseases and allergy); regulation of hematopoiesis(e.g. for treating anaemia or as adjunct to chemotherapy); stimulationor growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. fortreating wounds, stimulation of follicle stimulating hormone (forcontrol of fertility); chemotactic and chemokinetic activities (e.g. fortreating infections, tumors); hemostatic or thrombolytic activity (e.g.for treating haemopbilia, cardiac infarction etc.); anti-inflammatoryactivity (e.g. for treating septic shock, Crohn's disease); asantimicrobials; for treating psoriasis or other hyperproliferativediseases; for regulation of metabolism, and behaviour. Also contemplatedis the use of the corresponding nucleic acid in gene therapy procedures.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:60 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 1177 of SEQ ID NO:60, b is an integer of 15 to 1191, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:60, and where the b is greater than or equal to a+14.

[0255] Features of Protein Encoded by Gene No: 51

[0256] The translation product of this gene shares sequence homologywith human Sop2p-like protein which is important in cytoskeletonstructure. In one embodiment, polypeptides of the invention comprise thesequence SLHKINSVSQISVLSGGKAKCS QFCTTGMDOGMSIWDVKSLfSALKDLKI (SEQ IDNO:282). Polynucleotides encoding this polypeptide are also encompassedby the invention. This gene maps to chromosome 7. Therefore,polynucleotides of the invention can be used in linkage analysis as amarker for chromosome 7.

[0257] This gene is expressed primarily in immune and hematopoietictissues/cells and to a lesser extent in other tissues.

[0258] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,immunological and hematopoietic disorders and inflammation. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune and hematopoletic systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues and cell types (e.g., immune andhematopoietic tissue/cells, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual having,such a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:171 as residues: Lys-49 toGln-54, Ala-61 to Arg-66, Lys-82 to Lys-37, Glu-126 to Val-133, His-136to Ee-141, Glu-175 to Ser-187, Asp-296 to Leu-296, Ala-298 to Ser-310.

[0259] The tissue distribution in immune tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of immunological, hematopoietic, andinflammatory disorders, e.g, immunodeficiency, autoimmunity,inflammation. Protein, as well as, antibodies directed against theprotain may show utility as a tissue-specific marker and/orimmunotherapy target for the above-listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:61 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1566 of SEQ ID NO:61, b is aninteger of 15 to 1580, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:61, and where the b is greaterthan or equal to a+14.

[0260] Features of Protein Encoded by Gene No: 52

[0261] The translation product of this gene shares sequence homologywith Caenorhabditis elegies R53.5 gene encoding a putative secretedprotein.

[0262] This gene is expressed primarily in endothelial cells, brain andseveral highly vascularized, and tumor tissues and to a lesser extent inother tissues.

[0263] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, aberrantangiogensis and tumorigenesis. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe vascular and neural systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., endothelial cells, brain and othertissue of the nervous system, and vascular tissue, and cancerous andwounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:172 as residues:Thr-43 to Asn-60, Thr-106 to Phe-115, Asp-122 to Arg-133, Ar-186 toAsp-192, Leu-211 to Lys-216.

[0264] The tissue distribution in vascular tissue combined with thehomology to a C. elegans secreted protein indicates that polynucleotidesand polypeptides corresponding to this gene are useful for diagnosis ortreatment of disorders of the vascular or central nervous system, e.g,.aberrant angiogensis, ischemia, neurodegeneration, stroke, etc. Protein,as well as, antibodies directed against the protein may show utility asa tumor marker and/or immunotherapy targets for the above listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:62 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1103 of SEQID NO:62, b is an integer of 15 to 1117, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:62, and wherethe b is greater than or equal to a+14.

[0265] Features of Protein Encoded by Gene No: 53

[0266] In one embodiment, polypeptides of the invention comprise thesequence EASKSSHAGLDLFSVAACHRF (SEQ ID NO:28 3). Polynucleotidesencoding this polypeptide are also encompassed by the invention. Whentested against Jurkat T-cell lines, supernatants removed from cellscontaining this gene activated the GAS pathway. Thus, it is likely thatthis gene activates T-cells through the Jaks-STAT signal transductionpathway. The Gamma Activating Sequence (GAS) is a promoter element foundupstream of many genes which are involved in the Jaks-STAT pathway. TheJaks-STAT pathway is a large, signal transduction pathway involved inthe differentiation and proliferation of cells. Therefore, activation ofthe Jaks-STAT pathway, reflected by the binding of the GAS element, canbe used to indicate proteins involved in the proliferation anddifferentiation of cells.

[0267] This gene is expressed primarily in T-cells and to a lesserextent in brain. Therefore, polynucleotides and polypeptides of theinvention are useful as reagents for differential identification of thetissue(s) or cell type(s) present in a biological sample and fordiagnosis of diseases and conditions, which include, but are not limitedto, lymphocytic disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe lymphoid system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues and cell types(e.g. immune, T-cells, or other blood cells, brain and other tissue ofthe nervous system, and cancerous and wounded tissues) or bodily fluids(e.g. lymph, serum, plasma, urine, synovial fluid or spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder. Preferred epitopes include those comprising asequence shown in SEQ ID NO:173 as residues: Pro-3 to Thr-S, Arg-s7 toAsp-46.

[0268] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for diagnosis,treatment, and cure of lymphocytic disorders. Alternatively, expressionwithin neural tissue suggests that the protein product of this clonewould be useful for the detection/treatment of neurodegenerative diseasestates, behavioural disorders, or inflammatory conditions such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, meningitis, encephalitis, demyelination diseases, peripheralneuropathies, neoplasia, trauma, congenital malformations, spinal cordinjuries, ischeria and infarction, aneurysms, hemorrhages,schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder,panic disorder, learning disabilities, ALS, psychoses, autism, andaltered bahaviors, including disorders in feeding, sleep patterns,balance, and preception. In addition, the gene or gene product may alsoplay a role in the treatment and/or detection of developmental disordersassociated with the developing embryo, sexually-linked disorders, ordisorders of the cardiovascular system. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:63 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 347 of SEQ. ID NO:63, b is aninteger of 15 to 361, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:63, and where the b is greaterthan or equal to a+14.

[0269] Features of Protein Encoded by Gene No: 54

[0270] The translation product of this gene shares sequence homologywith secreted cartilage matrix protein, a major component of theextracellular matrix of nonarticular cartilage which is thought to beimportant in cartilage structure. In specific embodiments, polypeptidesof the invention comprise the sequence: RCKKCTEGPIDLVFVIDGSKSLGEEIEVVKQF (SEQ ID NO:292); VTGIIDSLTISPKAARVGL LQYSTQVH(SEQ ID NO:285); TEFTLRNFNSAKDMKKAVAHMKYM (SEQ ID NO:236);GKGSMTGLALKHMFERSFTQGEGARPF (SEQ ID NO:287); STRVPRAAIVFRDGPAQDDVSEWASKAKAANGITMYAVGVGKAIE (SEQ ID NO:288);EELQEIASEPTNKHLFYAEDFSTNIDEISEKLKKGICEALEDS (SEQ ID NO :289);TQRLEEMTQRM (SEQ ID NO:290); PQGCPEQPLH (SEQ ID NO:29 1);YMGKOSMTGLALKHNVFERSFT (SEQ ID NO:284), GWETLPKKDVCKSTHHGCEHICVNNGNSYICKCSXGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVYKQFVTGHDSLTISPKLARVGLLQYSTQVHEFTLRNFNSAKDMKKAVASMKYMIGKGSIMTOLALKILIFERSFTQGEGCARPPQGCPEQPLCSPTDGLRMTSPSOPVKPRPMVSLCMLLG (SEQ ID NO:293), or KFYPRRRGQALSTRVPRAAIVDGRAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTNfDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLE EMTQRNIEALENRLRYR(SEQ ID NO:294). Polynucleotides encoding these polypeptides are alsoencompassed by the invention. The gene encoding the disclosed cDNA isbelieved to reside on chromosome 8. Accordingly, polynucleotides relatedto this invention are useful as a marker in linkage analysis forchromosome S.

[0271] This gene is expressed primarily in placenta, infant brain,prostate, fetal lung and to a lesser extent in endometrium and fetaltissues.

[0272] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, abnormalplacenta and pregnancy, disorder and injury in brain, prostate, andvasculature. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thereproduction, neuronal, and vascular systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. developing, placenta, brain andother tissue of the nervous system, prostate, lung and endometrium, andcancerous and wounded tissues) or bodily fluids (e.g. amniotic fluid,seminal fluid, pulmonary surfactant, or sputum, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0273] The tissue distribution in placental tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis, treatment, and cure of abnormalities in placenta andpregnancy, disorder and injury in brain, prostate, and vasculature.Similarly, the homology to the cartilage matrix protein suggests thatthe protein product of this clone would be useful for the treatment,diagnosis, and/or prevention of various skin disorders includingcongenital disorders (i.e. nevi, moles, freckles, Mongolian spots,hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses,Bowen's disease, basal cell carcinoma, squamous cell carcinoma,malignant melanoma, Paget's disease, mycosis fungicides, and Kaposi'ssarcoma), injuries and inflammation of the skin (i.e. wounds, rashes,prickly heat disorder, psoriasis, dermatitis), atherosclerosis,uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupuserythematosus, vitiligo, dermatomyositis, morphea, scleroderma,pemphigoid, and pemphigus), keloids, striae, erythema, petechiae,purpura, and xanthelasma. In addition, such disorders may predisposeincreased susceptibility to viral and bacterial infections of the skin(i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpeszoster, boils, cellulitis, erysipelas, impetigo, tinea, athletes foot,and ringworm). Moreover, the protein product of this clone may also beuseful for the treatment or diagnosis of various connective tissuedisorders such as arthritis, trauma, tendonitis, chrondomalacia andinflammation, autoimmune disorders such as rheumatoid arthritis, lupus,scleroderma, and dermatomyositis as well as dwarfism, spinaldeformation, and specific joint abnormalities as well aschondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familialosteoarthitits, Atelosteocgenesis type II, metaphyseal chondrodysplasiatype Schmid). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:64 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1654 of SEQ ID NO:64, b is an integer of 15 to1668, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:64, and where the b is greater than or equalto a+14.

[0274] Features of Protein Encoded by Gene No: 55

[0275] The translation product of this gene is the human cytology ofbovine and hamster CII-3, a succinate-ubiquinone oxidoreductase complexII membrane-intrinsic subunit, which is thought to be important inmitochondrial electron transport chain during metabolism. In specificembodiments, the polypeptides of the invention compriseMAALLLRHVGRHCLRAHFSPQLCIRNAVPLGTTAKEEMERFWNKNIG SINRPLSPHITIYS (SEQ IDNO:295); VFPLIVIYHTWINGIRHLMWDLGKGLKIPQL YQSG (SEQ ID NO:296);MAALLLREVGRHCLRAH (SEQ ID NO:297); VKSLCL GPALIHTAKFAL (SEQ ID NO:298);VFPLMYHTWINGTRELNfLGKGL (SEQ ID NO:299).

[0276] This gene is expressed in 8-week old early stage human.

[0277] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,metabolic or developmental disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the reproductive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., developmental, metabolic, cancerousand wounded tissues) or bodily fluids (e.g., lymph, amniotic fluid,serum, plasma, urine, synovial fluid or spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0278] The tissue distribution in fetal tissue combined with thehomology to a metabolic protein indicates that polynucleotides andpolypeptides corresponding to this gene are useful for diagnosis,treatment, and cure of metabolism disorders. Similarly, expressionwithin embryonic tissue and other cellular sources marked byproliferating cells suggests that this protein may play a role in theregulation of cellular division, and may show utility in the diagnosisand treatment of cancer and other proliferative disorders. Similarly,embryonic development also involves decisions involving celldifferentiation and/or apoptosis in pattern formation. Thus this proteinmay also be involved in apoptosis or tissue differentiation and couldagain be useful in cancer therapy. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Protein, as well as,antibodies directed against the protain may show utility as atissue-specific marker and/or immunotherapy target for the above-listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:65 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1339 of SEQID NO:65, b is an integer of 15 to 1353, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:65, and wherethe b is greater than or equal to a+14.

[0279] Features of Protein Encoded by Gene No: 56

[0280] This gene is expressed primarily in umbilical vein endothelialcells, human ovarian tumor cells, human meningima cells, and humanJurkat membrane bound polysomes. In specific embodiments, polypeptidesof the invention comprise the amino acid sequence: RVVRPFAPKERCVKIFQGNV(SEQ ID NO:300); HNFEKNLL RCSWSPDGSKLAAGSADRFVYV (SEQ ID NO:301);WDTTSRRILYILPG HAGSINEVAFHPDEPI (SEQ ID NO :302),YQGLGLRQNILTYTMRGHAIDSVTGLSLSSEGSYLLSNAMDNTVRVDVRPFAPKERCVKIFQGNVHNFEKNLLRCSWSPDGSKLAAGSADRFVYVWDTTSRRILYKLPGHAGSBEVAFHPDEPIIISASS DKRLYMGEIQ (SEQID NO:303), or RKKAAIQTFQNTYQVLAVTFNDTSD QIISGGIDNDIKVWDCARTS (SEQ IDNO:304). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0281] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,inflammation, immune and cardiovascular disorders and urogenitalneoplasias, and developmental disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of these tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the immune, neurological, urogenital,reproductive system and vascular systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., blood cells, cells, endothelialcells, ovary and other reproductive tissue, developmental, meningima,and cancerous and wounded tissues) or bodily fluids (e.g. amnioticfluid, seminal fluid, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample-taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:143 as residues: Phe-71 toArg-76, Pro-82 to His-87, Glu-103 to Ala-111.

[0282] The tissue distribution in immune cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of immune disorders including:leukemias, lymphomas, auto-immune, immuno-suppressive (e.g.transplantation) and immunodeficiencies (e.g. AIDS) and hematopoieticdisorders. In addition, expression in ovarian tumor cells suggests thatpolynucleotides and polypeptides corresponding to this gene are usefulfor study, diagnosis, and treatment of ovarian tumors, and other tumorsand neoplasias. Further, endothelial cell expression suggests a role incadiovascular or respiratory/pulmonary disorders or infections (asthma,pulmonary edema, pneumonia). Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:66 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 997 of SEQ ID NO:66, b is aninteger of 15 to 1011, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:66, and where the b is greaterthan or equal to a+14.

[0283] Features of Protein Encoded by Gene No: 57

[0284] The translation product of this gene shares sequence homologywith type I collagen. In specific embodiments, the polypeptides of theinvention comprise the sequence: GRIPAPAPSVPAGPDSR (SEQ ID NO:308);VRGRTVLRPGLDAEPE LSPE (SEQ ID NO:305); EQRVLERKLKKERKKEERQ (SEQ IDNO:306); ARRSG AELAWDYLCRWAQKHKIFQKTRQIVLLLHMYDSDKVPDEKFSTLLAYLE GLQGR(SEQ ID NO:309); and/or RLREAGLVAQHPP (SEQ ID NO:307). Polynucleotidesencoding these polypeptides are also encompassed by the invention.Polynucleotides of the invention do not comprise the nucleic acidsequence shown as Genbank Accession No. gil073921HUNIRETPIGA, which ishereby incorporated herein by reference.

[0285] This gene is expressed primarily in epididymus, prostate cellline (LNCAP), and pituitary gland; and to a lesser extent in many othertissues.

[0286] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,abnormalities of the epididymus, prostate (especially prostate cancer),pituitary gland, or other reproductive, urogenital, or endocrinedisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of themale reproductive system and neuroendocrine system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues and cell types (e.g., epididymus and otherreproductive tissue, prostate, and pituitary gland, and cancerous andwounded tissues) or bodily fluids (e.g. seminal fluid, serum, plasma,urine, synovial fluid or spiral fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0287] The tissue distribution and homology to type I collagen,indicates that polynucleotides and polypeptides corresponding to thisgene are useful for diagnosis and treatment of abnormalities of theepididymus, prostate (especially prostate cancer), and pituitary gland.Similarly, the protein product of this clone may also be useful for thetreatment or diagnosis of various connective tissue disorders such asarthritis, trauma, tendonitis, chrondomalacia and inflammation,autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma,and dermatomyositis as well as dwarfism, spinal deformation, andspecific joint abnormalities as well as chondrodysplasias (i.e.spondyloepiphyseal dysplasia congenita, familial osteoarthritis,Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:67 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is anyinteger-between 1 to 1179 of SEQ ID NO:67, b is an integer of 15 to1193. where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:67, and where the b is greater than or equalto a+14.

[0288] Features of Protein Encoded by Gene No: 53

[0289] This gene is expressed primarily in the frontal cortex of thebrain from a schizophrenic individual.

[0290] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, neuraldisorders, particularly neurodegenerative disorders such asschizophrenia. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thenervous system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues and cell types(e.g., brain and other tissue of the nervous system, and cancerous andwounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0291] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thedetection/treatment of neurodegenerative disease states, behaviouraldisorders, or inflammatory conditions such as Alzheimers Disease,Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis,encephalitis, demyelinating diseases, peripheral neuropathies,neoplasia, trauma, congenital malformations, spinal cord injuries,ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, panic disorder,learning disabilities, ALS, psychoses, autism, and altered bahaviors,including disorders in feeding, sleep patterns, balance, and preception.In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, sexually-linked disorders, or disorders of thecardiovascular system. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues. Many polynucleotide sequences,such as EST sequences, are publicly available and accessible throughsequence databases. Some of these sequences are related to SEQ ID NO:68and may have been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 546 of SEQ ID NO:68, b is an integer of 15 to560, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:68, and where the b is greater than or equalto a+14.

[0292] Features of Protein Encoded by Gene No: 59

[0293] The polypeptide encoded by Gene 59 is homologous to human surface4 integral membrane protein. In specific embodiments, the polypeptidesof the invention comprise the sequence:TGCVLVLSRNQYACFGLFGIIALQTIAYSILWDLKFLMRN (SEQ ID NO:10);SRSEGKSIFAGVPTNIRESSPKQYMlQLGORVLLVLMFMTLLH FDASFFSIVQNTVG (SEQ IDNO:311); GTAEDFADQFLRVTKQYLPHVARLCLIST FLEDGRMIFQWSEQRDYIDTVNCGYLLAS(SEQ ID NO:312); LMRNESRS (SEQ ID NO:314); ASFLLSRTSWGTA (SEQ IDNO:315); ASFLLSRTSW GTALMIL (SEQ ID NO:313), ASFLLSRTSWGTALNIIL (SEQ IDNO:316), PSFTL TPASFLLSRTSWGTALMILVAIGFKTKLAALTLVVLFALTVYFNAFPVYKPMHDFLKYDFFQT (SEQ ID NO:317), RTEPPPGTSCGGRSGCGRRRAPASERASEPSRASRRRRHOPERPDGHGRGLRRPVPPCHKAVPAPRGAPLSDQHLPGGRHPYVVPVERAARLHRHHLELRLPAGLVLRLPQAGTXTGCVLVLSRNFVQYACFGLFGIIALQTIAYSILWDLKFLMRNLALCGGGLLLLLAESRSEGKSMFAGVPTMRESSPKQYMQLGGRVLLVLMFITLLHFDASFFSIVQNIVGHSSDDFSGHWF (SEQ ID NO:318),GXSRRRALPVBAAAGAGADGREPASERASRkEPPAVANIGQNDLGTAEDFADQFLRVTKQYLPHVARCLISTFLEDGnVFQWSEQRDYIDT TWNCGOYLLASSFVFLNLLGX(SEQ ID NO:319), or WVFLFLLALGGLGPDSGRCLCREGRISGIYQLILAKQFLRFFCFMWETDLNLILCCTLYLSCV (SEQ ID NO:320).Polynucleotides encoding these polypeptides are also encompassed by theinvention. The gene encoding the disclosed cDNA is believed to reside onchromosome 9. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 9.

[0294] This gene is expressed primarily in Hodgkin's lymphoma and lung;and to a lesser extent in many other human tissues.

[0295] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immunedisorders, particularly Hodgkin's lymphoma, tumors or otherabnormalities of the lung. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune and respiratory systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. hematopoietic, lymphoid tissue, andpulmonary tissue, and cancerous and wounded tissues) or bodily fluids(e.g. lymph, pulmonary surfactant or sputum, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:179 as residues:Met-20 to Trp-27.

[0296] The tissue distribution in immune tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of Hodgkin's lymphoma, tumors or otherabnormalities of the lung. Similarly, expression of this clone withinimmune tissues, particularly Hodgkin's lymphoma, suggests a role in theregulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer (e.g. by boostingimmune responses). Since the gene is expressed in cells of lymphoidorigin, the natural gene product may be involved in immune functions.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immunodeficiency diseases such as AIDS,leukemia, rheumatoid arthritis, granulomatous disease, inflammatorybowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis,hypersensitivities, such as T-cell mediated cytotoxicity; immunefactions to transplanted organs and tissues, such as host-versus-graftand graft-versus-host diseases, or autoimmunity disorders, such asautoimmune infertility, lense tissue injury, demyelination, systemiclupus erythematosis, drug induced hemolytic anemia, rheumatoidarthritis, Sjogren's disease, scleroderma and tissues. In addition, thisgene product may have commercial utility in the expansion of stem cellsand committed progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Many polynucleotide sequences, such as EST sequences, are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:69 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1643 of SEQID NO:69, b is an integer of 15 to 1657, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:69, and wherethe b is greater than or equal to a+14.

[0297] Features of Protein Encoded by Gene No: 60

[0298] The gene encoding the disclosed cDNA is believed to reside onchromosome 17. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 17.

[0299] This gene is expressed primarily in bone cancer and stomachcancer, and to a lesser extent in many other tissues.

[0300] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, bonecancer and stomach cancer. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe bone, and the stomach, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues(e.g., bone, and stomach, skeletal, gastrointestinal, and cancerous andwounded tissues) or bodily fluids (e.g. lymph, chyme, serum, plasma,urine, synovial fluid or spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0301] The tissue distribution in skeletal tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of skeletal or gastrointestinal disorders,particularly cancer. Similarly, the expression of this gene product inskeletal tissue would suggest a role in the detection and treatment ofdisorders and conditions affecting the skeletal system, in particularosteoporosis, bone cancer, as well as, disorders afflicting connectivetissues (e.g. arthritis, trauma, tendonitis, chrondomalacia andinflammation), such as in the diagnosis or treatment of variousautoimmune disorders such as rheumatoid arthritis, lupus, scleroderma,and dermatomyositis as well as dwarfism, spinal deformation, andspecific joint abnormalities as well as chondrodysplasias (i.e.spondyloepiphyseal dysplasia congenita, familial osteoarthritis,Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:70 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 697 of SEQ ID NO:70, b is an integer of 15 to 711, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:70, and where the b is greater than or equal to a+14.

[0302] Features of Protein Encoded by Gene No: 61

[0303] The gene encoding the disclosed cDNA is believed to reside on theX chromosome. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for the X chromosome.

[0304] This gene is expressed primarily in epididymus, and lymph node ofbreast cancer, and to a lesser extent in many other tissues.

[0305] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,abnormalities of the epididymus, and breast cancer or other reproductiveconditions. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theepididymus and breast, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues and celltypes (e.g., epididymus and other reproductive tissue, lymphoid tissue,and mammary tissue, and cancerous and wounded tissues) or bodily fluids(e.g. lymph, breast milk, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:181 as residues: Arg-57 toSer-65.

[0306] The tissue distribution in reproductive tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of abnormalities of the epididymus, breastcancer, or other reproductive disorders. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:71 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 921 of SEQ ID NO:71, b is aninteger of 15 to 935, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:71, and where the b is greaterthan or equal to a+14.

[0307] Features of Protein Encoded by Gene No: 62

[0308] The translation product of this gene appears to be the humanhomolog of bovine NADH dehydrogenase which is thought to be important incellular metabolism. In specific embodiments, the polypeptides of theinvention comprise the amino acid sequence:SMSALTRLASFARVGGRLFRSGCARTAGDGGVRHAGGGVHEEPRYRQFPQLTRSQVFQSEFFSGLMWFWILWRFWHDSEEVLOEFPYPDPSQWTDEEL GIPPDDED (SEQ IDNO:321), or fragments thereof. Polynucleotides encoding this polypeptideare also encompassed by the invention.

[0309] This gene is expressed in larynx tumor, lymph node, brainamygdala, human cardiomyopathy, and retina.

[0310] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, diseasesaffecting cellular metabolism. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe nervous system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues and cell types(e.g., larynx, lymphoid tissue, endothelial, brain and other tissue ofthe nervous system, heart and cardiovascular tissue, and retina, andcancerous and wounded tissues) or bodily fluids (e.g. lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:182 as residues: Pro-42 to Thr-51, Pro-85 to Glu-95.

[0311] The tissue distribution and homology to NADH dehydrogenaseindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the treatment and diagnosis of diseases involvingcellular metabolism. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues. Many polynucleotide sequences,such as EST sequences, are publicly available and accessible throughsequence databases. Some of these sequences are related to SEQ ID NO:72and may have been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 490 of SEQ ID NO:72, b is an integer of 15 to504, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:72, and where the b is greater than or equalto a+14.

[0312] Features of Protein Encoded by Gene No: 63

[0313] This gene is expressed primarily in amygdala, and to a lesserextent in many other tissues.

[0314] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, neuraldisorders, particularly neurodegenerative disorders or abnormalities ofthe amygdala. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theamygdala, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues and cell types (e.g.neural, amygdala, and lymphoid tissue, and cancerous and woundedtissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:183 as residues:Gln-17 to Glu-29, Pro-41 to Phe-46, Ser-59 to Ile-70, Thr-97 to Leu-105.

[0315] The tissue distribution in neural tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of abnormalities of amygdala. Similarly,expression within neural tissues suggests that the protein product ofthis clone would be useful for the detection/treatment ofneurodegenerative disease states, behavioural disorders, or inflammatoryconditions such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, Tourette Syndrome, meningitis, encephalitis, demyelinatingdiseases, peripheral neuropathies, neoplasia, trauma, congenitalmalformations, spinal cord injuries, ischemia and infarction, aneurysms,hemorrhages, schizophrenia, mania, dementia, paranoia, obsessivecompulsive disorder, panic disorder, learning disabilities, ALS,psychoses, autism, and altered bahaviors, including disorders infeeding, sleep patterns, balance, and preception. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo,sexually-linked disorders, or disorders of the cardiovascular system.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:73 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 606 of SEQ ID NO:73, b is an integer of 15 to 620, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:73, and where the b is greater than or equal to a+14.

[0316] Features of Protein Encoded by Gene No: 64

[0317] This gene is expressed primarily in female bladder, and to alesser extent in chronic synovitis and hemangiopericytoma.

[0318] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,urogenital or skeletal disorders, particularly bladder cancer.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the unarytract, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,bladder, synovial tissue, and vascular tissue, and cancerous and woundedtissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:184 as residues:Pro-2 to Gln-7, Pro-27 to Phe-34.

[0319] The tissue distribution in urogenital tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treatments of defects of the urinary tract, especially bladdercancer. Alternatively, expression within synovitis tissue suggests arole in the detection and treatment of disorders and conditionsaffecting the skeletal system, in particular osteoporosis, bone cancer,as well as, disorders afflicting connective tissues such as arthritis,trauma, tendonitis, chrondomalacia, autoimmune disorders such asrheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well asdwarfism, spinal deformation, and specific joint abnormalities as wellas chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita,familial osteoarthritis, Atelosteogenesis type II, metaphysealchondrodysplasia type Schmid). Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:74 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 567 of SEQ ID NO:74, b is aninteger of 15 to 581, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:74, and where the b is greaterthan or equal to a+14.

[0320] Features of Protein Encoded by Gene No: 65

[0321] This gene is expressed primarily in fetal spleen, and to a lesserextent in hemangiopericytoma, thymus, and synovial sarcoma.

[0322] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, defectsof immune of hematopoietic systems. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune of hematopoietic systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g. immune, hematopoietic, spleen,vascular tissue, thymus, blood cells, and synovial tissue, and cancerousand wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid,serum, plasma, urine, synovial fluid or spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0323] The protein product of this gene is useful for treatment ofdefects of the immune or hematopoietic systems, because of the gene'sexpression in thymus and spleen. Similarly, the secreted protein canalso be used to determine biological activity, to raise antibodies, astissue markers, to isolate cognate ligands or receptors, to identifyagents that modulate their interactions and as nutritional supplements.It may also have a very wide range of biological activities. Typical ofthese are cytokine, cell proliferation/differentiation modulatingactivity or induction of other cytokines;immunostimulating/immunosuppressant activities (e.g. for treating humanimmunodeficiency virus infection, cancer, autoimmune diseases andallergy); regulation of hematopoiesis (e.g. for treating anaemia or asadjunct to chemotherapy); stimulation or growth of bone, cartilage,tendons, ligaments and/or nerves (e.g. for treating wounds, stimulationof follicle stimulating hormone (for control of fertility); chemotacticand chemokinetic activities (e.g. for treating infections, tumors);hemostatic or thrombolytic activity (e.g. for treating haemophilia,cardiac infarction etc.); anti-inflammatory activity (e.g. for treatingseptic shock, Crohn's disease); as antimicrobials; for treatingpsoriasis or other hyperproliferative diseases; for regulation ofmetabolism, and behaviour. Also contemplated is the use of thecorresponding nucleic acid in gene therapy procedures. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:75 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1829 of SEQID NO:75, b is an integer of 15 to 1843, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:75, and wherethe b is greater than or equal to a+14.

[0324] Features of Protein Encoded by Gene No: 66

[0325] This gene is expressed primarily in human pituitary and to alesser extent in placenta and fetal lung.

[0326] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,endocrine growth disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe endocrine system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., pituitary and other endocrine tissue, placenta, developmental andpulmonary tissue, and cancerous and wounded tissues) or bodily fluids(e.g. lymph, amniotic fluid, pulmonary surfactant or sputum, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:186 as residues: Val-38 to Asn-44, Gly-53 to Ser-65.

[0327] The tissue distribution in fetal tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treatment of disorders related to endocrine or pituitarydysfunction, particularly growth disorders. Similarly, expression withinfetal tissue and other cellular sources marked by proliferating cellssuggests that this protein may play a role in the regulation of cellulardivision, and may show utility in the diagnosis and treatment of cancerand other proliferative disorders. Similarly, embryonic development alsoinvolves decisions involving cell differentiation and/or apoptosis inpattern formation. Thus this protein may also be involved in apoptosisor tissue differentiation and could again be useful in cancer therapy.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:76 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 1427 of SEQ ID NO:76, b is an integer of 15 to 1441, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:76, and where the b is greater than or equal to a+14.

[0328] Features of Protein Encoded by Gene No: 67

[0329] The translation product of this gene shares sequence homologywith a Caenorhabditis elegans gene. In specific embodiments, thepolypeptides of the invention comprise the sequence: DPRRPNKVLRYKPPPSECNPALDDPTP (SEQ ID NO:323); DYMNLLGMIFSMCGLMLKLKWCAWAVA VYCS (SEQ IDNO:324); FISFANSRSSEDTKQIlMSSF (SEQ ID NO:322); and/or MLSISAVVMSYLQNPQPNITPPW (SEQ ID NO:325). Polynucleotides encoding these polypeptidesare also encompassed by the invention. The gene encoding the disclosedcDNA is believed to reside on chromosome 19. Accordingly,polynucleotides related to this invention are useful as a marker inlinkage analysis for chromosome 19.

[0330] This gene is expressed primarily in primary breast cancer andlymph node breast cancer and to a lesser extent in adult brain, lungcancer, colon cancer, epithelioid sarcoma, and Caco-2 cell line.

[0331] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,reproductive, neural, or endothelial disorders, particularly cancer.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the cancer andtumor tissues, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.mammary tissue, lymphoid tissue, brain and other tissue of the nervoussystem, lung, colon, and epithelium, and cancerous and wounded tissues)or bodily fluids (e.g. lymph, pulmonary surfactant or sputum, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:187 as residues: Asn-34 to Lys-42.

[0332] The tissue distribution in a variety of cancer tissues indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for treatment and diagnosis of a variety of cancer and tumortypes. Protein, as well as, antibodies directed against the protein mayshow utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:77 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 896 of SEQ ID NO:77, b is an integer of 15 to910, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:77, and where the b is greater than or equalto a+14.

[0333] Features of Protein Encoded by Gene No: 68

[0334] The translation product of this gene shares sequence homologywith steroid membrane binding protein. The translation product of thisgene has recently been published as progesterone binding protein. SeeGenbank AJ002030. Preferred polypeptides encoded by this gene comprisethe following amino acid sequence:AAGDGDVKLGTLGSGSESSNDGGSESPGDAGAAAXGGGWAAAALALLTG GGE (SEQ ID NO:326),or STHASGRAVMAAGDGDVKLOTLGSGSESSNDGG SESPGDAGAAAXGGGWAAAKLALLTOGGE (SEQID NO:327). The gene encoding the disclosed cDNA is believed to resideon chromosome 4. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 4.

[0335] This gene is expressed primarily in breast, and to a lesserextent in placenta and fetal tissue.

[0336] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, breastcancer or developmental disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of breast or fetal tissues, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. reproductive, mammary tissue,placenta, and fetal tissue, and cancerous and wounded tissues) or bodilyfluids (e.g. lymph, amniotic fluid, breast milk,, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., expresision level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:188 as residues:Pro-43 to Asp-49, Gln-54 to Pro-64, Asp-110 to Asp-118, Lys-138 toTyr-143, Pro-150 to Asp-170.

[0337] The tissue distribution in reproductive tissues combined with thehomology to a steroid membrane binding protein and to progesteronebinding protein indicates that the protein products of this gene areuseful for treatment of breast cancers, especially those caused byestrogen and progesterone binding. Similarly, expression within fetaltissues and other cellular sources marked by proliferating cellssuggests that this protein may play a role in the regulation of cellulardivision, and may show utility in the diagnosis and treatment of cancerand other proliferative disorders. Similarly, embryonic development alsoinvolves decisions involving cell differentiation and/or apoptosis inpattern formation. Thus this protein may also be involved in apoptosisor tissue differentiation and could again be useful in cancer therapy.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:78 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 2762 of SEQ ID NO:78, b is an integer of 15 to 2776, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:73, and where the b is greater than or equal to a+14.

[0338] Features of Protein Encoded by Gene No: 69

[0339] It is likely that the open reading frame containing, thepredicted signal peptide continues in the 5′ direction. Therefore,preferred polypeptides encoded by this gene comprise the following aminoacid sequence: AADNYGIPRACRiNSARSYGAAWLLLXPAGSSRPVEPTQDISISDQLGGQDVPVFRNLSLLVVGVCAVFSLLELGTRERRRPHAXEPOElTPLLAPATAQPLLLWHWLREXAFYQVGILYMITTRLIVNLSQTYMAMYLTYSLHLPKKFIATIPLVMYLSGFLSSFLMKPLNKCIGRN (SEQ ID NO:328).

[0340] This gene is expressed primarily in macrophage (GM-CSF treated),and to a lesser extent in monocytes and dendritic cells.

[0341] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immuneor hematopoietic disorders, particularly inflammation and infection.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immunesystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues and cell types (e.g.immune, macrophages and other blood cells, and dendritic cells, andcancerous and wounded tissues) or bodily fluids (e.g. lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0342] The tissue distribution in immune tissue indicates that theprotein products of this gene are useful for treatment of infection orinflammation or other events or defects involving the immune system.Similarly, the tissue distribution suggests a role in the regulation ofthe proliferation; survival; differentiation; and/or activation ofpotentially all hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-raft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scieroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:79 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To Listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1473 of SEQ ID NO:79, b is aninteger of 15 to 1487, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:79, and where the b is greaterthan or equal to a+14.

[0343] Features of Protein Encoded by Gene No: 70

[0344] This gene was found to have homology to a conserved human 15 kDaselenoprotein (See Genbank Accession No. gil3095111 (AF051894)) whichmay be involved in the regulation of important cellular functions suchas metabolism or cell cycle regulation.

[0345] This gene is expressed primarily in adult brain and to a lesserextent in thyroid, 12 week old early stage human, and stromal cellTF274.

[0346] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,neurological or neuro-endocrine diseases. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the central nervous or endocrine systems, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues and cell types (e.g., brain and other tissueof the nervous system, developmental, immune, thyroid, endocrine, andstromal cells, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in, healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:190 as residues: Pro-65 toCys-71.

[0347] The tissue distribution in neural tissue indicates that theprotein products of this gene are useful for treatment and diagnosis ofneurological diseases or metabolic conditions involving theneuro-endocrine system. Similarly, the protein product of this clonewould be useful for the detection/treatment of neurodegenerative diseasestates, behavioural disorders, or inflammatory conditions such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, meningitis, encephalitis, demyelinating diseases, peripheralneuropathies, neoplasia, trauma, congenital malformations, spinal cordinjuries, ischermia and infarction, aneurysms, hemorrhages,schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder,panic disorder, learning disabilities, ALS, psychoses, autism, andaltered bahaviors, including disorders in feeding, sleep patterns,balance, and preception. In addition, the gene or gene product may alsoplay a role in the treatment and/or detection of developmental disordersassociated with the developing embryo, sexually-linked disorders, ordisorders of the cardiovascular system. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:80 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1549 of SEQ ID NO:30, b is aninteger of 15 to 1563, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:80, and where the b is greaterthan or equal to a+14.

[0348] Features of Protein Encoded by Gene No: 71

[0349] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: CTLAiWXLGHCDPRRCTORKLARGLVRCLRLGHRFGGLVLSPVGKQYASPADRQLVAQSGVAVTDCSWARLDETPFGK (SEQ ID NO:329).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0350] This gene is expressed in helper T-cells and, to a lesser extentin adult brain and adult testes.

[0351] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, immunedisorders, meningitis or reproductive problems. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune, neural and reproductive systems, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues and cell types (e.g., T-cells and otherblood cells, brain and other tissue of the nervous system, testes andother reproductive tissue, and cancerous and wounded tissues) or bodilyfluids (e.g. seminal fluid, lymph, serum, plasma, urine, synovial fluidor spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:191 as residues:Val-18 to Tyr-24, Ala-89 to Asp-99, Asp-104 to Ala-117, Leu-121 toPro-136.

[0352] The tissue distribution in immune cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of immune and reproductive disorders.Similarly, the secreted protein can also be used to determine biologicalactivity, to raise antibodies, as tissue markers, to isolate cognateligands or receptors, to identify agents that modulate theirinteractions and as nutritional supplements. It may also have a verywide range of biological activities. Typical of these are cytokine, cellproliferation/differentiation modulating activity or induction of othercytokines; immunostimulating/immunosuppressant activities (e.g. fortreating human immunodeficiency virus infection, cancer, autoimmunediseases and allergy); regulation of hematopoiesis (e.g. for treatinganaemia or as adjunct to chemotherapy); stimulation or growth of bone,cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds,stimulation of follicle stimulating hormone (for control of fertility);chemotactic and chemokinetic activities (e.g. for treating infections,tumors); hemostatic or thrombolytic activity (e.g. for treatinghaemopbilia, cardiac infarction etc.); anti-inflammatory activity (e.g.for treating septic shock, Crohn's disease); as antimicrobials; fortreating psoriasis or other hyperproliferative diseases; for regulationof metabolism, and behaviour. Also contemplated is the use of thecorresponding nucleic acid in gene therapy procedures. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:81 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1006 of SEQID NO:81, b is an integer of 15 to 1020, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:81, and wherethe b is greater than or equal to a+14.

[0353] Features of Protein Encoded by Gene No: 72

[0354] The translated polypeptide of this contig has a high degree ofidentity with the Ob Receptor-Associated Protein deposited as GenbankAccession No. 2266638. No function has been determined for the ObReceptor-Associated Protein, however it is expressed upon stimulation ofthe Ob Receptor by Leptin. In specific embodiments, polypeptides of theinvention comprise the following amino acid sequence:SGRARSDVTAMAGGIKALISLSFGGAIGLMFLMLGCALPIYNKYWPLFVLFFYILSPIPYCIARRLVDDTDA (SEQ ID -NO:330). Polynucleotides encoding thesepolypeptides are also encompassed by the invention.

[0355] This gene is expressed in T-cells and to a lesser extent inendothelial and bone marrow cells.

[0356] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, acutelymphoblastic leukemia, hematapoetic disorders. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune and hematapoetic systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues and cell types (e.g. immune, T-cells and other bloodcells, endothelial cells, and bone marrow, and cancerous and woundedtissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:192 as residues:Ser-61 to Trp-70.

[0357] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for treatment anddiagnosis of leukemia and other disorders of the primary immune system.In addition, since this gene appears to be related to the ObReceptor-Related Protein, it is likely that this polypeptide is alsoinvolved in the Ob/Leptin signal transduction cascade. As a result, thisprotein may be of use in the molecular diagnosis and therapeuticintervention of obesity and related disorders. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues. Manypolynucleotide sequences, such as EST sequences, are publicly availableand accessible through sequence databases. Some of these sequences arerelated to SEQ ID NO:82 and may have been publicly available prior toconception of the present invention. Preferably, such relatedpolynucleotides are specifically excluded from the scope of the presentinvention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 756 of SEQID NO:82, b is an integer of 15 to 770, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:82, and wherethe b is greater than or equal to a+14.

[0358] Features of Protein Encoded by Gene No: 73

[0359] The translation product of this contig has homology with furin, aprotein thought to be a key endopeptidase in the constitutive secretorypathway. The identification and initial characterization of Furin wasreported by Takahasi and colleagues (Biochem Biophys Res Commun 1993September 15;195(2):1019-1026).

[0360] This gene is expressed primarily in neutrophilia.

[0361] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, diseasesof the immune system such as allergies, wound healing and antigenrecognition. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues and cell types (e.g.immune tissues, neutrophilia and other blood cells, and cancerous andwounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0362] The tissue distribution in neutrophilia indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treatment of allergies or other immune disorders since neutrophiliaare an important part of an allergic response. Further, since thisprotein appears to be related to furin, it can be used diagnosticallyand therapeutically to treat secretory protein processing disorders.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Many polynucleotide sequences, such as EST sequences,are publicly available and accessible through sequence databases. Someof these sequences are related to SEQ ID NO:83 and may have beenpublicly available prior to conception of the present invention.Preferably, such related polynucleotides are specifically excluded fromthe scope of the present invention. To list every related sequence wouldbe cumbersome. Accordingly, preferably excluded from the presentinvention are one or more polynucleotides comprising a nucleotidesequence described by the general formula of a-b, where a is any integerbetween 1 to 467 of SEQ ID NO:83, b is an integer of 15 to 48 I, whereboth a and b correspond to the positions of nucleotide residues shown inSEQ ID NO:83, and where the b is greater than or equal to a+14.

[0363] Features of Protein Encoded by Gene No: 74

[0364] This gene is expressed in the frontal cortex.

[0365] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, of themotor activity and sensory functions that involve the central nervoussystem. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thecentral nervous system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., brain and other tissue of the nervous system, and cancerousand wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0366] The tissue distribution in neural tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection and treatment of neural disorders that affectcognitive functions. Similarly, the protein product of this clone wouldbe useful for the detection/treatment of neurodegenerative diseasestates, behavioural disorders, or inflammatory conditions such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, meningitis, encephalitis, demyelinating diseases, peripheralneuropathies, neoplasia, trauma, congenital malformations, spinal cordinjuries, ischemia and infarction, aneurysms, hemorrhages,schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder,panic disorder, learning disabilities, ALS, psychoses, autism, andaltered bahaviors, including disorders in feeding, sleep patterns,balance, and preception. In addition, the gene or gene product may alsoplay a role in the treatment and/or detection of developmental disordersassociated with the developing embryo, sexually-linked disorders, ordisorders of the cardiovascular system. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:84 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 630 of SEQ ID NO:84, b is aninteger of 15 to 644, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:84, and where the b is greaterthan or equal to a+14.

[0367] Features of Protein Encoded by Gene No: 75

[0368] The translation product of this gene shares sequence homologywith inorganic pyrophophatase which is thought to be important in thecatalysis the hydrolysis of diphosphate bonds, chiefly in nucleoside di-and triphosphates and essential enzymes that are important forcontrolling the cellular levels of inorganic pyrophosphate (PPi). Thebovine homolog of this gene has been identified by Yang and Wensel (J.Biol. Chem. 267:24641-24647 (1992)). In specific embodiments,polypeptides of the invention comprise the following amino acidsequence: ARVRXRGALSLSVGAACGLVALWQRRRQDSCT (SEQ ID NO:33 1).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0369] This gene is expressed in osteocIastoma cells and to a lesserextent in epithelial cells.

[0370] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,osteoporosis and other skeletal disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the skeletal system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., bone, and epithelial cells, andcancerous and wounded tissues) or bodily fluids (e.g. lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:195 as residues: Lys-22 to Tyr-28, Asp-64 to Lys-77, Pro-86 toIle-91, Gin-99 to Pro-119, Tyr-169 to Asp-174, Lys-176 to Gly-181,Trp-189 to Asn-202, Lys-233 to Gly-239, Ser-250 to Asp-257.

[0371] The tissue distribution in osteoclastoma cells and homology toinorganic pyrophophatase indicates that polynucleotides and polypeptidescorresponding to this gene are useful for treatment and diagnosis ofosteoporosis through the removal of bone by demineralization. Similarly,the expression of this gene product in osteoclastoma cells would suggesta role in the detection and treatment of disorders and conditionsaffecting the skeletal system, in particular osteoporosis, bone cancer,as well as, disorders afflicting connective tissues such as arthritis,trauma, tendonitis, chrondomalacia, autoimmune disorders such asrheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well asdwarfism, spinal deformation, and specific joint abnormalities as wellas chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita,familial osteoarthritis, Atelosteogenesis type II, metaphysealchondrodysplasia type Schmid). Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:85 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be ccumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1337 of SEQ ID NO:85, b is aninteger of 15 to 1351, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:85, and where the b is greaterthan or equal to a+14.

[0372] Features of Protein Encoded by Gene No: 76

[0373] The translation product of this gene shares exact sequencehomology with ATP sulfurylase/APS kinase (GenBank Accession No. 2673862)which is thought to be important in biosynthesis of the activatedsulfate donor, adenosine 3′-phosphate 5′-phosphosulfate, involves thesequential action of two enzyme activities: ATP sulfurylase, whichcatalyzes the formation of adenosine 5′-phosphosulfate (APS) from ATPand free sulfate, and APS kinase, which subsequently phosphorylates APSto produce adenosine 3′-phosphate 5′-phosphosulfate. In specificembodiments, polypeptides of the invention comprise the following aminoacid sequence: LSNNAQNWGIMQRATNVTYQAHHVSRNKRGQVVGTRGGFRGCTVWL (SEQ IDNO:332), VSMALEEYLVCHGIPCYTLDGDNIRQGLNKNLGFSPED (SEQ ID NO:333),TQDRNNARQIHEGASLPPFkFVDAPLHVCEQRDVKGLY (SEQ ID NO:334),FTGIDSEYEKPEAPELVLKTDSCDVNDCVQQVYLLQERD (SEQ ID NO:335),AETLPALKINKVDMQWVQVLAWEGWATPLNGFMREREYLQCL (SEQ ID NO:336),VPIVLTATHEDKERLDGCTFALIMYEGRRV (SEQ ID NO:337),IGGDLQVLDRVYNDOLDQYLTFTELKQIKDNLADAV (SEQ ID NO-338),GHALLMQDTHKQLLERGYRRPVLLLHPILGGWVTKDDDV (SEQ ID NO:339),MYAGFIEVQWHCRARMVAGANFVGRDPAGMPHETGKDL (SEQ ID NO:340),LTIVLKPGLITLEIVPFRVAAYNKKKKRLMIDEYDSEH (SEQ ID NO:341) or,GFMAPKAWTVLTEYYKSLE (SEQ ID NO:342). Polynucleotides encoding thesepolypeptides are also encompassed by the invention.

[0374] This gene is expressed in osteoclastoma cells and to a lesserextent in developmental tissues.

[0375] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,antibiotic resistant bacterial infections, osteoarthritis and other autoimmune diseases, or skeletal disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune or skeletal structure expression of this geneat significantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g. bone, and developmental tissues, andcancerous and wounded tissues) or bodily fluids (e.g. lymph, amnioticfluid, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:196 as residues: Asn-15 to Trp-20, Ser-36 to Gly-41,Pro-134 (93 to Val110, Pro-134 to Arg-143, Leu-173 to Arg-178, Ser-190to Ala-197, His-314 to Arg-319, Arg-354 to Asn-362, Asp-391 to Arg-397,Glu-402 to Asp-409, Asp-434 to Leu-439, Glu-441 to Arg-446, Gly-455 toAsp-462, Pro- 528 to His-541, Asn-566 to Arg-571, Tyr-574 to Glu-589,Thr-589 to Glu-603.

[0376] The tissue distribution and homology to ATP sulfurylase/APSkinase indicates that polynucleotides and polypeptides corresponding tothis gene are useful for the treatment or detection of autoimmunediseases. Similarly, the expression of this gene product in synoviumwould suggest a role in the detection and treatment of disorders andconditions affecting the skeletal system, in particular osteoporosis,bone cancer, as well as, disorders afflicting connective tissues such asarthritis, trauma, tendonitis, chrondomalacia, autoimmune disorders suchas rheumatoid arthritis, lupus, scieroderma, and dermatomyositis as wellas dwarfism, spinal deformation, and specific joint abnormalities aswell as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita,familial osteoarthritis, Atelosteogenesis type II, metaphysealchondrodysplasia type Schmid). Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:86 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 2513 of SEQ ID NO:86, b is aninteger of 15 to 2527, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:86, and where the b is greaterthan or equal to a+14.

[0377] Features of Protein Encoded by Gene No: 77

[0378] This polypeptide is identical to the SLP-76-associated proteinreported by Musci and colleagues (J. Biol. Chem. 272 (18), 11674-11677(1997)) and to the FYB protein reported by da Silva and coworkers (Proc.Natl. Acad. Scl. U.S.A. (1997) In press). These proteins have beenreported to be novel T-cell Proteins which bind FYN and SLP-76 andregulate IL-2 production. Preferred polypeptides encoded by this genecomprise the following amino acid sequence: RITDNPEGKWLGRTARGSYGYIKTTAVELXYDSLKLKKDSLGAPSRPIEDDQEVYDDVAEQDDISSHSQSGSGGIFPPPPDDDIYDGIEEEDADDGFPAPPKQLDMGDEVYDDVDTSDFPVSSAEMSQGTNVGKAKTEEKDLKKLKKQXKEXKDFRKKFKYDGEIRVLYSTKVTTSITSKKWGTRDLQVKPGESLEVIQTTDDTKVLCINEEGKYGYVLRSYLADNDGEIYDDIADGC IYDND (SEQ IDNO:343).

[0379] This gene is expressed in CD34 positive cells (hematopoieticprogenitor cells) and to a lesser extent in adult spleen derived from achronic lymphocytic leukemia patient.

[0380] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, chroniclymphocytic leukemia; hematopoietic disorders. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune and hematopoietic systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., T-cells and other blood cells,bone marrow, hematopoietic cells, and spleen, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Further, nucleic acidsand polypeptides of the present invention are useful both diagnosticallyand therapeutically in the intervention of immune and other disorders inwhich the ability to alter IL-2 expression is desired. Preferredepitopes include those comprising, a sequence shown in SEQ ID NO:191 asresidues: Ala-17 to Lys-37, Val-39 to Ser-45, Lys-59 to His-70, Arg-90to Leu-95, Lys-97 to Lys-107, Ser-117 to Leu-124, Phe-133 to Ser-133,Trp-146 to Leu-167, Pro-175 to Asn-185, Lys-190 to Ser-211, Pro-213 toSer-222, His-230 to Pro-235, Pro-240 to Pro-246, Pro-253 to Gly-261,Leu-271 to Leu-303, Leu-305 to Leu-326, Lys-343 to Leu-349, Thr-363 toLeu-371, Arg-373 to Tyr-381, Tyr-391 to Leu-401, Pro-404 to Val-414,Ser-426 to Ser-432, Dle-448 to Ser-457, Gln-462 to Trp-468, Lys-477 toSer-501, Asp-518 to Ser-523, Ala-541 to Gln-554.

[0381] The tissue distribution in immune cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment of a variety of hematopoletic disorders. The notedexpression of this gene in hematopoietic progenitor cell—as determinedby its expression on CD34 positive hematopoietic stem and progenitorcells—indicates that it plays a critical role in the expansion orproliferation of hematopoietic stem/progenitor cells, as well as in thedifferentiation of the various blood cell lineages. Thus it could beuseful in the reconstitution of the hematopoietic system of patientswith leukemias and other hematopoletic diseases. Protein, as well as,antibodies directed against the protain may show utility as atissue-specific marker and/or immunotherapy target for the above-listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:87 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 2552 of SEQID NO:87, b is an integer of 15 to 2566, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:87, and wherethe b is greater than or equal to a+14.

[0382] Features of Protein Encoded by Gene No: 78

[0383] This gene is homologous to heparin cofactor II (HCII) which is a66-kDa plasma glycoprotein that inhibits thrombin rapidly in thepresence of dermatan sulfate or heparin.

[0384] This gene is expressed in apoptotic and anergic T-cells.

[0385] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,thrombopienia T-cell lymphomas; Hodgkin's lymphoma. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system—most notably theT-cell compartment, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues and cell types(e.g., T-cells and other blood cells, and lymphoid tissue, and cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid or spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0386] The homology to heparin cofactor II (HCII) and the tissuedistribution indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the treatment and diagnosis ofhematopoietic disorders particularly in thrombopoesis, most notably ofthe T-cell compartment. This could include immune modulation,inflammation, immune surveillance, graft rejection, and autoimmunity.Protein, as well as, antibodies directed against the protain may showutility as a tissue-specific marker and/or immunotherapy target for theabove-listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:98 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 526 of SEQ ID NO:88, b is an integer of 15 to540, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:88, and where the b is greater than or equalto a+14.

[0387] Features of Protein Encoded by Gene No: 79

[0388] The translation product of this gene shares sequence homologywith a mouse protein believed to represent an integral membrane protein.

[0389] This gene is expressed in fetal cochlea and epididymus and to alesser extent in adult spleen and osteoclastoma.

[0390] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,osteoclasioma: disorders of the inner ear; male fertility disorders.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the inner ear;male reproductive tract; bone; and immune systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., cochlea, epididymus and otherreproductive tissue, spleen, immune tissue, and bone, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, seminal fluid, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:199 as residues: Lys-13 to Gly-23, Cys-38 to Asp-43, Gly-48 toTrp-53, Cys-223 to Ile-237, He-240 to Ser-246.

[0391] The tissue distribution in reproductive tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment of hearing and fertility disorders. Likewise, it mayhave a role in the modulation of immune function and in the treatment ofosteoporosis. Protein, as well as, antibodies directed against theprotain may show utility as a tissue-specific marker and/orimmunotherapy target for the above-listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:89 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1849 of SEQ ID NO:89, b is aninteger of 15 to 1963, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:89, and where the b is greaterthan or equal to a+14.

[0392] Features of Protein Encoded by Gene No: 80

[0393] The translation product of this gene shares sequence homologywith reticulocalbin which is thought to be important in the binding ofcalcium, particularly within the endoplasmic reticulum.

[0394] This gene is expressed in endothelial cells and stromal cells andto a lesser extent in osteoblasts, osteoclasts, and T-cells.

[0395] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,osteoporosis; osteoclastomas; T-cell lymphomas; Hodgkin's disease.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of thevasculature, bone, and immune systems—particularly the T-cellcompartments, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues and cell types(e.g., endothelial cells, stromal cells, bone, T-cells and other bloodcells, and lymphoid tissue, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder. Preferred epitopes include thosecomprising a sequence shown in SEQ ID NO:200 as residues: Lys-20 toArg-27, Pro-32 to Asp-43, Leu-64 to Arg-72, Asp108 to Lys-114, Glu-128to Thr-133, Asp-139 to Phe-147, Thr-196 to Ala-204, Tyr-218 to Glu-228,Val-230 to Gln-236, Arg-241 to Lys-255, Glu-276 to Lys-287. The tissuedistribution and homology to reticulocalbin indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of bone disorders such as osteoporosis;the diagnosis and treatment of T-cell lymphomas and Hodgkin's lymphoma;and the treatment of diseases and defects of the vasculature, such asvascular leak syndrome and aberrant angiogensis that accompanies tumorgrowth. Protein, as well as, antibodies directed against the protain mayshow utility as a tissue-specific marker and/or immunotherapy target forthe above-listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:90 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 2464 of SEQ ID NO:90, b is an integer of 15 to2478, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:90, and where the b is greater than or equalto a+14.

[0396] Features of Protein Encoded by Gene No: 31

[0397] The translation product of this gene shares sequence homologywith a family of peptide transport genes—particularly the ALPTR2-B genefrom Arabidopsis—which are thought to be important in the uptake ofsmall peptides.

[0398] This gene is expressed in a number of fetal tissues, most notablylung, brain, cochlea, and liver/spleen, and to a lesser extent inosteoclastoma and endometrial tumors.

[0399] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,osteoclastoma; endometrial tumors; cancer; leukemias. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the bone and endometrium, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., fetal tissue, pulmonarytissue, bone, brain and other tissue of the nervous system, cochlea,liver, and spleen, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, pulmonary surfactant or sputum, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO. 201 as residues:Lys-186 to Asn-199, Pro-202 to Ala-207. The tissue distribution in fetaltissues combined with the homology to peptide transport proteinsindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the control of cell proliferation, owing to itsstrong expression in fetal tissues undergoing active cell division, aswell as its expression in a variety of tumors or cancers of adulttissues. Potentially, it may regulate the uptake of peptides thatstimulate cell proliferation. This gene product may also be useful instimulating the uptake of a variety of peptide-based drug compounds.Protein, as well as, antibodies directed against the protain may showutility as a tissue-specific marker and/or immunotherapy target for theabove-listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:91 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 2044 of SEQ ID NO:91, b is an integer of 15 to2058, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:91, and where the b is greater than or equalto a+14.

[0400] Features of Protein Encoded by Gene No: 82

[0401] This gene is expressed in fetal liver and spleen and to a lesserextent in endothelial cells.

[0402] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, cancerand tumors of a hematopoietic and/or endothelial cell origin; leukemias.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immunesystem and/or vasculature, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues andcell types (e.g., liver, spleen, endothelial cells, vascular tissue, andtissue and cells of the immune system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, amniotic fluid, bile, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.Preferred epitopes include those comprising a sequence shown in SEQ IDNO:202 as residues: Met-1 to Asp-9, Ara-66 to Gly-76, Asp-164 toArg-171.

[0403] The tissue distribution in immune tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment of disorders of the immune system. Expression of thisgene product in both fetal liver/spleen and endothelial cells indicatesthat it may be expressed in the hemangioblast, the progenitor cell forboth the immune system and the vasculature. Thus, it is most likelyexpressed in hematopoietic stem cells, and may be useful for theexpansion of hematopoietic stem and progenitor cells in conjunction withcancer treatment for a variety of leukemias. Protein, as well as,antibodies directed against the protain may show utility as atissue-specific marker and/or immunotherapy target for the above-listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:92 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 1397 of SEQID NO:92, b is an integer of 15 to 1411, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:92, and wherethe b is greater than or equal to a+14.

[0404] Features of Protein Encoded by Gene No: 84

[0405] The translation product of this gene shares sequence homologywith NADH dehydrogenase which is thought to be important in cellularmetabolism.

[0406] This gene is expressed in fetal dura mater and to a lesser extentin T-cells and hypothalamus.

[0407] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to, diseasesaffecting cellular metabolism. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe nervous system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues and cell types(e.g., fetal tissue, T-cells and other blood cells, and brain and othertissue of the nervous system, and cancerous and wounded tissues) orbodily fluids (e.g., amniotic fluid, lymph, serum, plasma, urine,synovial fluid or spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:204 as residues:Pro-27 to Gln-32, Arg-42 to Glu-51.

[0408] The tissue distribution and homology to NADH dehydrogenaseindicates that polynucleotides and polypeptides corresponding to thisgene are useful for treatment and diagnosis of diseases involvingcellular metabolism. Protein, as well as, antibodies directed againstthe protain may show utility as a tissue-specific marker and/orimmunotherapy target for the above-listed tissues. Mary polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:94 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 743 of SEQ ID NO:94, b is aninteger of 15 to 757, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:94, and where the b is greaterthan or equal to a+14.

[0409] Features of Protein Encoded by Gene No: 85

[0410] The translation product of this gene shares sequence homologywith I-TRAF, a novel TNF receptor associated factor (TRMF)-interactingprotein that regulates TNF receptor-mediated signal transduction. Thisprotein is thought to be important in regulating the cellular responseto tumor necrosis factor (TNF), which is an important mediator ofinflammation.

[0411] This gene is expressed in endothelial cells and to a lesserextent in glioblastoma and osteoblastoma.

[0412] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,inflammation; glioblastoma and osteoblastoma. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in Providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues and cell types (e.g., endothelial cells, bone, and glialcells and tissue of the nervous system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid or spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:205 as residues:Glu-15 to Tbr-22, Glu-46 to Leu-62, Arg-103 to Glu-119, Gln-127 toGlu-132, Asn-152 to Trp-158, Gln-191 to Gln-210, Glu-264 to Thr-271,Tyr-282 to Leu-288, Trp-319 to Thr-331, Glu-335 to Ser-348, Ser-353 toSer-358, Asp-382 to Asn-392.

[0413] The tissue distribution in endothelial cells combined with thehomology to the I-TRAF protein indicates that polynucleotides andpolypeptides corresponding to this gene are useful for treatment anddiagnosis of inflammatory diseases, including rheumatoid arthritis,sepsis, inflammatory bowel disease, and psoriasis, particularly wheretumor necrosis factor is known to be involved. Protein, as well as,antibodies directed against the protain may show utility as atissue-specific marker and/or immunotherapy target for the above-listedtissues. Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:95 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a-b, where a is any integer between 1 to 2380 of SEQID NO:95, b is an integer of 15 to 2394, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:95, and wherethe b is greater than or equal to a+14.

[0414] Features of Protein Encoded by Gene No: 86

[0415] This gene has homology with a candidate gene involved in X-linkedRetinopathy reported by Wong and colleagues (Genomics 15:467-471(1993)).

[0416] This gene is expressed in a T-cell Line.

[0417] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions, which include, but are not limited to,inflammation and autoimmune diseases; T-cell lymphona. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues and cell types (e.g, T-cells and other blood cells,and cancerous and wounded tissues) or bodily fluids (e.g, lymph, serum,plasma, urine, synovial fluid or spinal fluid) or another tissue or cellsample taken from an individual having such a disorder, relative to thestandard gene expression level, i.e, the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0418] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for treatment anddiagnosis of inflammatory disorders such as sepsis, inflammatory boweldisease, psoriasis, and rheumatoid arthritis as well as autoimmunedisease such as lupus. It could also be useful in immune modulation andin the process of immune surveillance. The present invention can be useddiagnostically and therapeutically to treat X-linked Retinopathy.Protein, as well as, antibodies directed against the protain may showutility as a tissue-specific marker and/or immunotherapy target for theabove-listed tissues. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:96 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the General formula of a-b, where a isany integer between 1 to 658 of SEQ ID NO:96, b is an integer of 15 to672, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:96, and where the b is greater than or equalto a+14.

[0419] Features of Protein Encoded by Gene No: 87

[0420] This gene is expressed in human brain tissue. Therefore,polynucleotides and polypeptides of the invention are useful as reagentsfor differential identification of the tissue(s) or cell type(s) presentin a biological sample and for diagnosis of diseases and conditions,which include, but are not limited to, brain disorders;neurodegenerative disorders; tumors of a brain origin. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous system, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues (e.g., brain and other tissue of the nervoussystem, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid or spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder. Preferred epitopes include those comprising a sequenceshown in SEQ ID NO:211 as residues: Cys-32 to Tyr-38. Preferred epitopesinclude those comprising a sequence shown in SEQ ID NO:207 as residues:Cys-32 to Tyr-38.

[0421] The tissue distribution in neural tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treatment and diagnosis of CNS disorders such as epilepsy, paranoia,depression, Alzheimer's disease, and schizophrenia. It could be usefulin the survival and/or proliferation of neurons and could effectneuronal regeneration. Protein, as well as, antibodies directed againstthe protain may show utility as a tissue-specific marker and/orimmunotherapy target for the above-listed tissues. Many polynucleotidesequences, such as EST sequences, are publicly available and accessiblethrough sequence databases. Some of these sequences are related to SEQID NO:11 and may have been publicly available prior to conception of thepresent invention. Preferably, such related polynucleotides arespecifically excluded from the scope of the present invention. To listevery related sequence would be cumbersome. Accordingly, preferablyexcluded from the present invention are one or more polynucleotidescomprising a nucleotide sequence described by the general formula ofa-b, where a is any integer between 1 to 1665 of SEQ ID NO:11, b is aninteger of 15 to 1679, where both a and b correspond to the positions ofnucleotide residues shown in SEQ ID NO:11, and where the b is greaterthan or equal to a+14. Many polynucleotide sequences, such as ESTsequences, are publicly available and accessible through sequencedatabases. Some of these sequences are related to SEQ ID NO:97 and mayhave been publicly available prior to conception of the presentinvention. Preferably, such related polynucleotides are specificallyexcluded from the scope of the present invention. To list every relatedsequence would be cumbersome. Accordingly, preferably excluded from thepresent invention are one or more polynucleotides comprising anucleotide sequence described by the general formula of a-b, where a isany integer between 1 to 1405 of SEQ ID NO:97, b is an integer of 15 to1419, where both a and b correspond to the positions of nucleotideresidues shown in SEQ ID NO:97, and where the b is greater than or equalto a+14. 5′ NT NT of AA First Last ATCC SEQ 5′ NT 3′ NT 5′ NT First SEQAA AA First AA Last Deposit ID Total of of of AA of ID of of of AA GenecDNA Nr and NO: NT Clone Clone Start Signal NO: Sig Sig Secreted of No.Clone ID Date Vector X Seq. Seq. Seq. Codon Pep Y Pep Pep Portion ORF 1HAGEW82 97923 Uni-ZAP XR 11 1679 247 1607 353 353 121 1 31 03/07/97209071  05/22/97 2 HAGFY16 97923 Uni-ZAP XR 12 1963 209 1922 251 251 1221 28 29 198 03/07/97 209071  05/22/97 2 HAGFY16 97923 Uni-ZAP XR 98 183087 1786 128 128 208 1 26 27 45 03/07/97 209071  05/22/97 3 HALAA60 97923Uni-ZAP XR 13 1212 1 1212 99 99 123 1 24 25 39 03/07/97 209071  05/22/974 HAPBL78 97923 Uni-ZAP XR 14 2061 882 2061 900 900 124 1 22 23 2303/07/97 209071  05/22/97 5 HASAV70 97923 Uni-ZAP XR 15 1412 10 733 103103 125 1 20 21 110 03/07/97 209071  05/22/97 6 HBNAF22 97923 Uni-ZAP XR16 1052 276 880 538 538 126 1 23 24 63 03/07/97 209071  05/22/97 7HBNBL77 97923 Uni-ZAP XR 17 683 1 683 181 181 127 1 30 03/07/97 209071 05/22/97 8 HCDDR90 97923 Uni-ZAP XR 18 1054 86 1007 86 86 128 1 23 24 5303/07/97 209071  05/22/97 9 HCEEF50 97923 Uni-ZAP XR 19 1393 132 1393192 192 129 1 17 18 57 03/07/97 209071  05/22/97 10 HCEMU42 97923Uni-ZAP XR 20 1215 277 1070 401 401 130 1 18 19 216 03/07/97 209071 05/22/97 11 HCENE16 97923 Uni-ZAP XR 21 2042 614 2011 793 793 131 1 2627 49 03/07/97 209071  05/22/97 12 HMSJJ74 97923 Uni-ZAP XR 22 1872 211872 69 69 132 1 23 24 68 03/07/97 209071  05/22/97 13 HCUBF15 97923 ZAPExpress 23 289 1 289 89 89 133 1 29 30 52 03/07/97 209071  05/22/97 14HE2DE47 97923 Uni-ZAP XR 24 3533 2821 3532 808 808 134 1 30 31 54003/07/97 209071  05/22/97 14 HE2DE47 97923 Uni-ZAP XR 99 1145 435 1115515 515 209 1 22 23 81 03/07/97 209071  05/22/97 15 HKMLH01 97923pBluescript 25 1148 171 907 196 196 135 1 26 27 57 03/07/97 15 HE6DG3497923 Uni-ZAP XR 100 734 25 734 295 295 210 1 36 37 49 03/07/97 209071 05/22/97 16 HE9DG49 97923 Uni-ZAP XR 26 717 1 717 70 70 136 1 27 28 20103/07/97 209071  05/22/97 16 HE9DG49 97923 Uni-ZAP XR 101 713 17 713 7878 211 1 28 29 203 03/07/97 209071  05/22/97 17 HELBA06 97923 Uni-ZAP XR27 1099 1 1099 38 38 137 1 22 23 216 03/07/97 209071  05/22/97 17HELBA06 97923 Uni-ZAP XR 102 1080 1 1080 149 149 212 1 25 26 18603/07/97 209071  05/22/97 18 HSLFM29 97923 Uni-ZAP XR 28 941 171 941 128128 138 1 42 43 102 03/07/97 209071  05/22/97 19 HELBW38 97923 Uni-ZAPXR 29 756 62 756 294 294 139 1 30 31 112 03/07/97 209071  05/22/97 20HETHN28 97923 Uni-ZAP XR 30 2100 408 2093 496 496 140 1 20 03/07/97209071  05/22/97 21 HFCDK17 97923 Uni-ZAP XR 31 1448 475 1392 567 567141 1 30 03/07/97 209071  05/22/97 22 HFEAF41 97923 Uni-ZAP XR 32 456 1409 21 21 142 1 28 29 99 03/07/97 209071  05/22/97 23 HFKFL13 97923Uni-ZAP XR 33 1326 1 1322 210 210 143 1 8 03/07/97 209071  05/22/97 24HFSBG13 97923 Uni-ZAP XR 34 710 1 710 242 242 144 1 16 17 39 03/07/97209071  05/22/97 25 HFTBE43 97923 Uni-ZAP XR 35 1188 110 1161 178 178145 1 26 27 131 03/07/97 209071  05/22/97 26 HFTDJ36 97923 Uni-ZAP XR 36956 1 938 144 144 146 1 21 22 32 03/07/97 209071  05/22/97 27 HKTAC7797924 Uni-ZAP XR 37 1603 974 1581 1104 1104 147 1 14 03/07/97 28 HLHSH3697924 pBluescript 38 1089 55 1067 209 148 1 8 03/07/97 29 HLHSV96 97924pBluescript 39 629 1 629 119 119 149 1 32 33 68 03/07/97 30 HLQBQ8697924 Lambda ZAP 40 1964 408 1793 581 581 150 1 26 03/07/97 II 31HLTBX31 97924 Uni-ZAP XR 41 1522 13 1123 126 126 151 1 32 33 19503/07/97 32 HLTCJ63 97924 Uni-ZAP XR 42 875 1 875 43 43 152 1 18 19 9103/07/97 33 HMKAH44 97924 pSport1 43 843 1 843 171 171 153 1 30 31 3103/07/97 34 HMQAJ64 97924 Uni-ZAP XR 44 489 3 489 55 55 154 1 19 20 9003/07/97 34 HMQAJ64 97924 Uni-ZAP XR 103 489 6 489 58 58 213 1 22 23 9003/07/97 35 HOABG65 97924 Uni-ZAP XR 45 534 1 534 17 17 155 1 18 19 8903/07/97 36 HODCL36 97924 Uni-ZAP XR 46 1374 1 1374 15 15 156 1 20 21174 03/07/97 36 HODCL36 97924 Uni-ZAP XR 104 1529 40 1399 54 54 214 1 2728 48 03/07/97 37 HODCL50 97924 Uni-ZAP XR 47 596 1 596 269 269 157 1 2728 45 03/07/97 38 HODCV74 97924 Uni-ZAP XR 48 851 99 822 170 170 158 123 03/07/97 39 HODCZ16 97924 Uni-ZAP XR 49 2020 569 2020 638 638 159 117 18 70 03/07/97 40 HTOEU03 97924 Uni-ZAP XR 50 2432 848 2432 99 99 1601 19 20 323 03/07/97 40 HTOEU03 97924 Uni-ZAP XR 105 2435 849 2435 928928 215 1 31 32 70 03/07/97 41 HPBCJ74 97924 pBluescript 51 2340 16272340 150 150 161 1 60 61 320 03/07/97 SK- 41 HPBCJ74 97924 pBluescript106 805 92 791 239 239 216 1 21 22 83 03/07/97 SK- 42 HPMBU33 97924Uni-ZAP XR 52 601 188 601 432 432 162 1 31 03/07/97 43 HSAUL66 97924Uni-ZAP XR 53 359 1 337 142 142 163 1 18 19 72 03/07/97 44 HSIDQ18 97924Uni-ZAP XR 54 1141 1 1141 25 25 164 1 30 31 281 03/07/97 44 HSIDQ1897924 Uni-ZAP XR 107 1166 21 1166 433 433 217 1 30 31 43 03/07/97 45HSJBB37 97924 Uni-ZAP XR 55 1560 413 1498 714 714 165 1 31 32 8103/07/97 46 HSJBQ79 97924 Uni-ZAP XR 56 1507 164 608 57 57 166 1 19 20327 03/07/97 46 HSJBQ79 97924 Uni-ZAP XR 108 586 4 586 35 35 218 1 23 24184 03/07/97 47 HTEGA76 97958 Uni-ZAP XR 57 450 1 450 90 90 167 1 43 4465 03/13/97 209072  05/22/97 48 HTEJN13 97958 Uni-ZAP XR 58 1147 1 1147163 163 168 1 15 16 159 03/13/97 209072  05/22/97 48 HTEJN13 97958Uni-ZAP XR 109 1134 1 1134 155 155 219 1 19 20 71 03/13/97 209072 05/22/97 49 HTHBL86 97958 Uni-ZAP XR 59 777 1 777 115 115 169 1 18 19123 03/13/97 209072  05/22/97 50 IITSFO71 97958 pBluescript 60 1191 48598 52 52 170 1 30 31 129 03/13/97 209072  05/22/97 50 HTSFO71 97958pBluescript 110 1333 594 1333 829 829 220 1 10 03/13/97 209072  05/22/9751 HAPNO80 209235  Uni-ZAP XR 61 1580 443 1554 114 114 171 1 1 2 37209/04/97 51 HAUCC47 97958 Uni-ZAP XR 111 1015 249 708 244 244 221 1 2829 138 03/13/97 52 HBMCL41 97958 pBluescript 62 1117 105 1034 182 182172 1 28 29 216 03/13/97 209072  05/22/97 53 HCFLD84 97958 pSport1 63361 1 361 97 97 173 1 32 33 55 03/13/97 209072  05/22/97 54 HE8EM6997958 Uni-ZAP XR 64 1668 1 1638 150 150 174 1 20 21 23 03/13/97 209072 05/22/97 55 HE8EZ48 97958 Uni-ZAP XR 65 1353 35 1303 231 231 175 1 33 34103 03/13/97 209072  05/22/97 56 HEBGF73 97958 Uni-ZAP XR 66 1011 6551011 703 703 176 1 38 39 48 03/13/97 209072  05/22/97 57 HFEBF41 97958Uni-ZAP XR 67 1193 267 1090 459 459 177 1 35 36 96 03/13/97 209072 05/22/97 58 HFRBU14 97958 Uni-ZAP XR 68 560 1 560 63 63 178 1 29 30 9503/13/97 209072  05/22/97 59 HFVGZ79 97958 pBluescript 69 1657 765 1581839 839 179 1 21 22 27 03/13/97 209072  05/22/97 60 HHGCM76 97958 LambdaZAP 70 711 8 711 270 270 180 1 22 23 89 03/13/97 II 209072  05/22/97 60HHGCM76 97958 Lambda ZAP 112 711 8 711 270 270 222 1 11 03/13/97 II209072  05/22/97 61 HHGCO88 97958 Lambda ZAP 71 935 111 935 272 272 1811 19 20 65 03/13/97 II 209072  05/22/97 62 HHGCP52 97958 Lambda ZAP 72504 113 484 45 45 182 1 15 16 105 03/13/97 II 209072  05/22/97 63HHGDB72 97958 Lambda ZAP 73 620 1 620 96 96 183 1 18 19 132 03/13/97 II209072  05/22/97 64 HHGDI71 97958 Lambda ZAP 74 581 156 581 248 248 1841 32 33 69 03/13/97 II 209072  05/22/97 65 HHSDI45 97958 Uni-ZAP XR 751843 537 1786 630 630 185 1 27 28 45 03/13/97 209072  05/22/97 66HHSEB66 97958 Uni-ZAP XR 76 1441 116 800 167 167 186 1 36 37 65 03/13/97209072  05/22/97 67 HAUAI83 97958 Uni-ZAP XR 77 910 1 886 253 253 187 137 38 49 03/13/97 209072  05/22/97 67 HJPAZ83 97958 Uni-ZAP XR 113 1076398 1076 575 223 1 11 12 23 03/13/97 209072  05/22/97 68 HLDBO49 97958pCMVSport 78 2776 18 1888 187 187 188 1 14 15 170 03/13/97 3.0 209072 05/22/97 69 HLDBQ19 209226  pCMVSport 79 1487 401 1487 534 534 189 1 2223 132 08/28/97 3.0 69 HLDBQ19 97958 pCMVSport 114 1525 401 1480 534 534224 1 22 23 66 03/13/97 3.0 209072  05/22/97 70 HMSGT42 97958 Uni-ZAP XR80 1563 33 1077 40 40 190 1 32 33 92 03/13/97 209072  05/22/97 71HMWIC78 97957 Uni-Zap XR 81 1020 18 780 238 238 191 1 23 24 176 03/13/97209073  05/22/97 72 HTTCT79 97957 Uni-ZAP XR 82 770 101 770 286 286 1921 26 27 70 03/13/97 209073  05/22/97 73 HNGJU84 97957 Uni-ZAP XR 83 4811 481 58 58 193 1 20 21 25 03/13/97 209073  05/22/97 74 HNTAC73 97957pCMVSport 84 644 1 623 14 14 194 1 25 26 73 03/13/97 3.0 209073 05/22/97 75 HOSEI45 97957 Uni-ZAP XR 85 1351 435 1284 98 98 195 1 12 13289 03/13/97 209073  05/22/97 75 HOSEI45 97957 Uni-ZAP XR 115 1350 4281283 545 225 1 28 03/13/97 209073  05/22/97 76 HOSFD58 97957 Uni-ZAP XR86 2527 290 1747 56 56 196 1 30 31 624 03/13/97 209073  05/22/97 76HOSFD58 97957 Uni-ZAP XR 116 2527 288 1747 477 477 226 1 32 33 6103/13/97 209073  05/22/97 77 HSAUM95 97957 Uni-ZAP XR 87 2566 1843 2566251 251 197 1 30 31 649 03/13/97 209073  05/22/97 77 HSAUM95 97957Uni-ZAP XR 117 1098 375 1098 677 677 227 1 21 22 29 03/13/97 209073 05/22/97 78 HSAUR67 97957 UNi-ZAP XR 88 540 1 540 83 83 198 1 32 33 5503/13/97 209073  05/22/97 79 HSKDI81 97957 Uni-ZAP XR 89 1863 152 1165188 188 199 1 11 12 266 03/13/97 209073  05/22/97 79 HSKDI81 97957Uni-ZAP XR 118 1679 152 1166 315 315 228 1 18 03/13/97 209073  05/22/9780 HSKDW91 97957 Uni-ZAP XR 90 2478 1149 2449 92 92 200 1 19 20 31503/13/97 209073  05/22/97 81 HTLEX50 97957 Uni-ZAP XR 91 2058 476 2058414 414 201 1 20 21 207 03/13/97 209073  05/22/97 82 HSKIIL65 97957pBluescript 92 1411 345 1411 157 157 202 1 69 70 195 03/13/97 209073 05/22/97 82 HSKHL65 97957 pBluescript 119 1411 345 1411 526 526 229 1 3738 72 03/13/97 209073  05/22/97 83 HHFGA11 97957 Uni-ZAP XR 93 2187 1472184 397 397 203 1 30 31 330 03/13/97 209073  05/22/97 83 HOEBX83 97957Uni-ZAP XR 120 2223 144 2136 198 198 230 1 20 21 142 03/13/97 209073 05/22/97 84 HWTBL40 97957 Uni-ZAP XR 94 757 524 608 445 445 204 1 20 2158 03/13/97 209073  05/22/97 85 HBXFG80 97957 ZAP Express 95 2394 4812394 523 523 205 1 1 2 392 03/13/97 209073  05/22/97 86 HCACY32 97957Uni-ZAP XR 96 672 1 672 117 117 206 1 21 22 26 03/13/97 209073  05/22/9787 HCEDO21 97957 Uni-Zap XR 97 1419 1 1419 207 207 207 1 20 21 3803/13/97 209073  05/22/97

[0422] Table 1 summarizes the information corresponding to each “GeneNo.” described above. The nucleotide sequence identified as “NT SEQ IDNO:X” was assembled from partially homologous (“overlapping”) sequencesobtained from the “cDNA clone ID” identified in Table 1 and, in somecases, from additional related DNA clones. The overlapping sequenceswere assembled into a single contiguous sequence of high redundancy(usually tree to five overlapping sequences at each nucleotideposition), resulting in a final sequence identified as SEQ ID NO:X.

[0423] The cDNA Clone ID was deposited on the date and given thecorresponding deposit number listed in “ATCC Deposit No:Z and Date.”Some of the deposits contain multiple different clones corresponding tothe same gene. “Vector” refers to the type of vector contained in thecDNA Clone ID.

[0424] “Total NT Seq.” refers to the total number of nucleotides in thecontig identified by “Gene No.” The deposited clone may contain all ormost of these sequences, reflected by the nucleotide position indicatedas “5′ NT of Clone Seq.” and the “3′ NT of Clone Seq.” of SEQ ID NO:X.The nucleotide position of SEQ ID NO:X of the putative start codon(methionine) is identified as “5′ NT of Stat Codon.” Similarly, thenucleotide position of SEQ ID NO:X of the predicted signal sequence isidentified as “5′ NT of First AA of Signal Pep.”

[0425] The translated amino acid sequence, beginning with themethionine, is identified as “AA SEQ ID NO:Y,” although other readingframes can also be easily translated using known molecular biologytechniques. The polypeptides produced by these alternative open readingframes are specifically contemplated by the present invention.

[0426] The first and last amino acid position of SEQ ID NO:Y of thepredicted signal peptide is identified as “First AA of Sig Pep” and“Last AA of Sig Pep.” The predicted first amino acid position of SEQ IDNO:Y of the secreted portion is identified as “Predicted First Ads ofSecreted Portion.” Finally, the amino acid position of SEQ ID NO:Y ofthe last amino acid in the open reading frame is identified as “Last AAof ORF.”

[0427] SEQ ID NO:X and the translated SEQ ID NO:Y are sufficientlyaccurate and otherwise suitable for a variety of uses well known in theart and described further below. For instance, SEQ ID NO:X is useful fordesigning nucleic acid hybridization probes that will detect nucleicacid sequences contained in SEQ ID NO:X or the cDNA contained in thedeposited clone. These probes will also hybridize to nucleic acidmolecules in biological samples, thereby enabling a variety of forensicand diagnostic methods of the invention. Similarly, polypeptidesidentified from. SEQ ID NO:Y may be used to generate antibodies whichbind specifically to the secreted proteins encoded by the cDNA clonesidentified in Table 1.

[0428] Nevertheless, DNA sequences generated by sequencing reactions cancontain sequencing errors. The errors exist as identified nucleotides,or as insertions or deletions of nucleotides in the generated DNAsequence. The erroneously inserted or deleted nucleotides cause frameshifts in the reading frames of the predicted amino acid sequence. Inthese cases, the predicted amino acid sequence diverges from the actual99.9% identical to the actual DNA sequence (for example, one baseinsertion or deletion in an open reading frame of over 1000 bases).

[0429] Accordingly, for those applications requiring precision in thenucleotide sequence or the amino acid sequence, the present inventionprovides not only the generated nucleotide sequence identified as SEQ IDNO:X and the predicted translated amino acid sequence identified as SEQID NO:Y, but also a sample of plasmid DNA containing a human cDNA of theinvention deposited with the ATCC, as set forth in Table 1. Thenucleotide sequence of each deposited clone can readily be determined bysequencing the deposited clone in accordance with known methods. Thepredicted amino acid sequence can then be verified from such deposits.Moreover, the amino acid sequence of the protein encoded by a particularclone can also be directly determined by peptide sequencing or byexpressing the protein in a suitable host cell containing the depositedhuman cDNA, collecting the protein, and determining its sequence.

[0430] The present invention also relates to the genes corresponding toSEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding genecan be isolated in accordance with known methods using the sequenceinformation disclosed herein. Such methods include preparing probes orprimers from the disclosed sequence and identifying or amplifying, thecorresponding gene from appropriate sources of genomic material.

[0431] Also provided in the present invention are species homologs.Species homologs may be isolated and identified by making suitableprobes or primers from the sequences provided herein and screening asuitable nucleic acid source for the desired homologue.

[0432] The polypeptides of the invention can be prepared in any suitablemanner. Such polypeptides include isolated naturally occurringpolypeptides, recombinantly produced polypeptides, syntheticallyproduced polypeptides, or polypeptides produced by a combination ofthese methods. Means for preparing such polypeptides are well understoodin the art.

[0433] The polypeptides may be in the form of the secreted protein,including the mature form, or nay be a part of a larger protein, such asa fusion protein (see below) It is often advantageous to include anadditional amino acid sequence which contains secretory or leadersequences, pro-sequences, sequences which aid in purification, such asmultiple histidine residues, or an additional sequence for stabilityduring recombinant production.

[0434] The polypeptides of the present invention are preferably providedin an isolated form, and preferably are substantially purified. Arecombinantly produced version of a polypeptide, including the secretedpolypeptide, can be substantially purified by the one-step methoddescribed in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides ofthe invention also can be purified from natural or recombinant sourcesusing antibodies of the invention raised against the secreted protein inmethods which are well known in the art.

[0435] Signal Sequences

[0436] Methods for predicting whether a protein has a signal sequence,as well as the cleavage point for that sequence, are available. Forinstance, the method of McGeoch, Virus Res. 3:271-236 (1985), uses theinformation from a short N-terminal charged region and a subsequentuncharged region of the complete (uncleaved) protein. The method of vonHeinje, Nucleic Acids Res. 14:468-4690 (1986) uses the information fromthe residues surrounding the cleavage site, typically residues −13 to+2, where +1 indicates the amino terminus of the secreted protein. Theaccuracy of predicting the cleavage points of known mammalian secretoryproteins for each of these methods is in the range of 75-80%. (vonHeinje, supra.) However, the two methods do not always produce the samepredicted cleavage point(s) for a given protein.

[0437] In the present case, the deduced amino acid sequence of thesecreted polypeptide was analyzed by a computer program called SignalP(Henrik Nielsen et al., Protein Engineering 10:1-6 (1997)), whichpredicts the cellular location of a protein based on the amino acidsequence. As part of this computational prediction of localization, themethods of McGeoch and von Heinje are incorporated. The analysis of theamino acid sequences of the secreted proteins described herein by thisprogram provided the results shown in Table 1.

[0438] As one of ordinary skill would appreciate, however, cleavagesites sometimes vary from organism to organism and cannot be predictedwvith absolute certainty. Accordingly, the present invention providessecreted polypeptides having a sequence shown in SEQ ID NO:Y which havean N-terminus beginning within 5 residues (i.e. + or  5 residues) of thepredicted cleavage point. Similarly, it is also recognized that in somecases, cleavage of the signal sequence from a secreted protein is notentirely uniform, resulting in more than one secreted species. Thesepolypeptides, and the polynucleotides encoding such polypeptides, arecontemplated by the present invention.

[0439] Moreover, the signal sequence identified by the above analysismay not necessarily predict the naturally occurring signal sequence. Forexample, the naturally occurring signal sequence may be further upstreamfrom the predicted signal sequence. However, it is likely that thepredicted signal sequence will be capable of directing the secretedprotein to the ER. These polypeptides, and the polynucleotides encodingsuch polypeptides, are contemplated by the present invention.

[0440] Polynucleotide and Polypeptide Variants

[0441] “Variant” refers to a polynucleotide or polypeptide differingfrom the polynucleotide or polypeptide of the present invention, butretaining essential properties thereof. Generally, variants are overallclosely similar, and, in many regions, identical to the polynucleotideor polypeptide of the present invention.

[0442] By a polynucleotide having a nucleotide sequence at least, forexample, 95% “identical” to a reference nucleotide sequence of thepresent invention, it is intended that the nucleotide sequence of thepolynucleotide is identical to the reference sequence except that thepolynucleotide sequence may include up to five point mutations per each100 nucleotides of the reference nucleotide sequence encoding thepolypeptide. In other words, to obtain a polynucleotide having anucleotide sequence at least 95% identical to a reference nucleotidesequence, up to 5% of the nucleotides in the reference sequence may bedeleted or substituted with another nucleotide, or a number ofnucleotides up to 5% of the total nucleotides in the reference sequencemay be inserted into the reference sequence. The query sequence may bean entire sequence shown in Table 1, the ORF (open reading frame), orany fragment specified as described herein.

[0443] As a practical matter, whether any particular nucleic acidmolecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99%identical to a nucleotide sequence of the presence invention can bedetermined conventionally using known computer programs. A preferredmethod for detecting the best overall match between a query sequence (asequence of the present invention) and a subject sequence, also referredto as a global sequence alignment, can be determined using the FASTDBcomputer program based on the algorithm of Brutlag et al. (Comp. App.Biosci. (1990) 6:237-245). In a sequence alignment the query and subjectsequences are both DNA sequences. An RNA sequence can be compared byconverting U's to T's. The result of said global sequence alignment isin percent identity. Preferred parameters used in a FASTDB alignment ofDNA sequences to calculate percent identify are: Matrix=Unitary,k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization GroupLength=0, Cutoff Score-=1, Gap Penalty=5, Gap Size Penalty 0.05, WindowSize=500 or the length of the subject nucleotide sequence, whichever isshorter.

[0444] If the subject sequence is shorter than the query sequencebecause of 5′ or 3′ deletions, not because of internal deletions, amanual correction must be made to the results. This is because theFASTDB program does not account for 5′ and 3 ′ truncations of thesubject sequence when calculating percent identity. For subjectsequences truncated at the 5′ or 3′ ends, relative to the the querysequence, the percent identity is corrected by calculating the number ofbases of the query sequence that are 5′ and 3′ of the subject sequence,which are not matched/aligned, as a percent of the total bases of thequery sequence. Whether a nucleotide is matched/aligned is determined byresults of the FASTDB sequence alignment. This percentage is thensubtracted from the percent identity, calculated by the above FASTDBprogram using the specified parameters, to arrive at a final percentidentity score. This corrected score is what is used for the purposes ofthe present invention. Only bases outside the 5′ and 3′ bases of thesubject sequence, as displayed by the FASTDB alignment, which are notmatched/aligned with the query sequence, are calculated for the purposesof manually adjusting the percent identity score.

[0445] For example, a 90 base subject sequence is aligned to a 100 basequery sequence to determine percent identity. The deletions occur at the5′ end of the subject sequence and therefore, the FASTDB alignment doesnot show a matched/alignment of the first 10 bases at 5′ end. The 10unpaired bases represent 10% of the sequence (number of bases at the 5′and 3′ ends not matched/total number of bases in the query sequence) so10% is subtracted from the percent identity score calculated by theFASTDB program. If the remaining 90 bases were perfectly matched thefinal percent identity would be 90%. In another example, a 90 basesubject sequence is compared with a 100 base query sequence. This timethe deletions are internal deletions so that there are no bases on the5′ or 3′ of the subject sequence which are not matched/aligned with thequery. In this case the percent identity calculated by FASTDB is notmanually corrected. Once again, only bases 5′ and 3′ of the subjectsequence which are not matched/aligned with the query sequence aremanually corrected for. No other manual corrections are to made for thepurposes of the present invention.

[0446] By a polypeptide having an amino acid sequence at least, forexample, 95% “identical” to a query amino acid sequence of the presentinvention, it is intended that the amino acid sequence of the subjectpolypeptide is identical to the query sequence except that the subjectpolypeptide sequence may include up to five amino acid alterations pereach 100 amino acids of the query amino acid sequence. In other words,to obtain a polypeptide having an amino acid sequence at least 95%identical to a query amino acid sequence, up to 5% of the amino acidresidues in the subject sequence may be inserted, deleted, (indels) orsubstituted with another amino acid. These alterations of the referencesequence may occur at the amino or carboxy terminal positions of thereference amino acid sequence or anywhere between those terminalpositions, interspersed either individually among residues in thereference sequence or in one or more contiguous groups within thereference sequence.

[0447] As a practical matter, whether any particular polypeptide is atleast 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, theamino acid sequences shown in Table 1 or to the amino acid sequenceencoded by deposited DNA clone can be determined conventionally usingknown computer programs. A preferred method for determine the bestoverall match between a query sequence (a sequence of the presentinvention) and a subject sequence, also referred to as a global sequencealignment, can be determined using the FASTDB computer program based onthe algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:23-7-245).In a sequence alignment the query and subject sequences are either bothnucleotide sequences or both amino acid sequences. The result of saidglobal sequence alignment is in percent identity. Preferred parametersused in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2,Mismatch Penalty=1, Joining Penalty=20, Randomizaton Group Length=0,Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap SizePenalty=0.05, Window Size=500 or the length of the subject amino acidsequence, whichever is shorter.

[0448] If the subject sequence is shorter than the query sequence due toN- or C- terminal deletions, not because of internal deletions, a manualcorrection must be made to the results. This is because the FASTDBprogram does not account for N- and C- terminal truncations of thesubject sequence when calculating global percent identity. For subjectsequences truncated at the N- and C-termini, relative to the the querysequence, the percent identity is corrected by calculating the number ofresidues of the query sequence that are N- and C-terminal of the subjectsequence, which are not matched/aligned with a corresponding subjectresidue, as a percent of he total bases of the query sequence. Whether aresidue is matched/aligned is determined by results of the FASTDBsequence alignment. This percentage is then subtracted from the percentidentity, calculated by the above FASTDB program using the specifiedparameters, to arrive at a final percent identity score. This finalpercent identity score is what is used for the purposes of the presentinvention. Only residues to the N- and C-termini of the subjectsequence, which are not matched/aligned with the query sequence, areconsidered for the purposes of manually adjusting the percent identityscore. That is, only query residue positions outside the farthest N- andC-terminal residues of the subject sequence.

[0449] For example, a 90 amino acid residue subject sequence is alignedwith a 100 residue query sequence to determine percent identity. Thedeletion occurs at the N-terminus of the subject sequence and therefore,the FASTDB alignment does not slow a matching/alignment of the first 10residues at the N-terminus. The 10 unpaired residues represent 10% ofthe sequence (number of residues at the N- and C- termini notmatched/total number of residues in the query sequence) so 10% issubtracted from the percent identity score calculated by the FASTDBprogram. If the remaining 90 residues were perfectly matched the finalpercent identity would be 90%. In another example, a 90 residue subjectsequence is to compared with a 100 residue query sequence. This time thedeletions are internal deletions so there are no residues at the N- orC- termini of the subject sequence which are not matched/aligned withthe query. In this case the percent identity calculated by FASTDB is notmanually corrected. Once again, only residue positions outside the N-and C-terminal ends of the subject sequence, as displayed in the FASTDBalignment, which are not matched/aligned with the query sequence aremanually corrected for. No other manual corrections are to made for thepurposes of the present invention.

[0450] The variants may contain alterations in the coding regions,non-coding regions, or both. Especially preferred are polynucleotidevariants containing alterations which produce silent substitutions,additions, or deletions, but do not alter the properties or activitiesof the encoded polypeptide. Nucleotide variants produced by silentsubstitutions due to the degeneracy of the genetic code are preferred.Moreover, variants in which 5-10, 1-5, or 1-2 amino acids aresubstituted, deleted, or added in any combination are also preferred.Polynucleotide variants can be produced for a variety of reasons, e.g.,to optimize codon expression for a particular host (chance codons in thehuman mRNA to those preferred by a bacterial host such as E. coli).

[0451] Naturally occurring variants are called “allelic variants,” andrefer to one of several alternate forms of a gene occupying a givenlocus or a chromosome of an organism. (Genes II, Lewin, B., ed., JohnWiley & Sons, New York (1985).) These allelic variants can vary ateither the polynucleotide and/or polypeptide level. Alternatively,non-naturally occuring variants may be produced by mutagenesistechniques or by direct synthesis.

[0452] Using known methods of protein engineering and recombinant DNAtechnology, variants may be generated to improve or alter thecharacteristics of the polypeptides of the present invention. Forinstance, one or more amino acids can be deleted from the N-terminus orC-terminus of the secreted protein without substantial loss ofbiological function. The authors of Ron et al., J. Biol. Chem. 268:2984-2988 (1993), reported variant KGF proteins having heparin bindingactivity even after deleting 3, 8, or 27 amino-terminal amino acidresidues. Similarly, Interferon gamma exhibited up to ten times higheractivity after deleting 8-10 amino acid residues from the carboxyterminus of this protein. (Dobeli et al. J. Biotechnology 7:199-216(1988).) Moreover, ample evidence demonstrates that variants oftenretain a biological activity similar to that of the naturally occurringprotein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111(1993)) conducted extensive mutational analysis of human cytokine IL-1a.They used random mutagenesis to generate over 3,500 individual IL-1amutants that averaged 2.5 amino acid chances per variant over the entirelength of the molecule. Multiple mutations were examined at everypossible amino acid position. The investigators found that “[m]ost ofthe molecule could be altered with little effect on either “binding orbiological activity.” (See, Abstract.) In fact, only 23 unique aminoacid sequences, out of more than 3,500 nucleotide sequences examined,produced a protein that significantly differed in activity fromwild-type.

[0453] Furthermore, even if deleting one or snore amino acids from theN-terminus or C-terminus of a polypeptide results in modification orloss of one or more biological functions, other biological activitiesmay still be retained. For example, the ability of a deletion variant toinduce and/or to bind antibodies which recognize the secreted form willlikely be retained when less than the majority of the residues of thesecreted form are removed from the N-terminus or C-terminus. Whether aparticular polypeptide acting N- or C-terminal residues of a proteinretains such immunogemic activities can readily be determined by routinemethods described herein and otherwise known in the art.

[0454] Thus, the invention further includes polypeptide variants whichshow substantial biological activity. Such variants include deletions,insertions, inversions, repeats, and substitutions selected according togeneral rules known in the art so as have little effect on activity. Forexample, guidance concerning how to make phenotypically silent aminoacid substitutions is provided in Bowie, J. U. et al., Science247:1306-1310 (1990), wherein the authors indicate that there are twomain strategies for studying the tolerance of an amino acid sequence tochange.

[0455] The first strategy exploits the tolerance of amino acidsubstitutions by natural selection during the process of evolution. Bycomparing amino acid sequences in different species, conserved aminoacids can be identified. These conserved amino acids are likelyimportant for protein function. In contrast, the amino acid positionswhere substitutions have been tolerated by natural selection indicatesthat these positions are not critical for protein function. Thus,positions tolerating amino acid substitution could be modified whilestill maintaining biological activity of the protein.

[0456] The second strategy uses genetic engineering to introduce aminoacid changes at specific positions of a cloned gene to identify regionscritical for protein function. For example, site directed mutagenesis oralanine-scanning mutagenesis (introduction of 5 single alanine mutationsat every residue in the molecule) can be used. (Cunningham and Wells,Science 244:1081-1085 (1989).) The resulting mutant molecules can thenbe tested for biological activity.

[0457] As the authors state, these two strategies have revealed thatproteins are surprisingly tolerant of amino acid substitutions Theauthors further indicate which amino acid changes are likely to bepermissive at certain amino acid positions in the protein. For example,most buried (within the tertiary structure of the protein) amino acidresidues require nonpolar side chains, whereas few features of surfaceside chains are generally conserved. Moreover, tolerated conservativeamino acid substitutions involve replacement of the aliphatic orhydrophobic amino acids Ala, Val, Leu and Ile; replacement of thehydroxyl residues Ser and Thr; replacement of the acidic residues Aspand Glu; replacement of the amide residues Asn and Gln, replacement ofthe basic residues Lys, Arg, and His; replacement of the aromaticresidues Phe, Tyr, and Trp, and replacement of the small-sized aminoacids Ala, Ser, Thr, Met, and Gly.

[0458] Besides conservative amino acid substitution, variants of thepresent invention include (i) substitutions with one or more of thenon-conserved amino acid residues, where the substituted amino acidresidues may or may not be one encoded by the genetic code, or (ii)substitution with one or more of amino acid residues having asubstituent group, or (iii) fusion of the mature polypeptide withanother compound, such as a compound to increase the stability and/orsolubility of the polypeptide (for example, polyethylene glycol), or(iv) fusion of the polypeptide with additional amino acids, such as anIgG Fc fusion region peptide, or leader or secretory sequence, or asequence facilitating purification. Such variant polypeptides are deemedto be within the scope of those skilled in the art from the teachingsherein.

[0459] For example, polypeptide variants containing amino acidsubstitutions of charged amino acids with other charged or neutral aminoacids may produce proteins with improved characteristics, such as lessaggregation. Aggregation of pharmaceutical formulations both reducesactivity and increases clearance due to the aggregate's immunogenicactivity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967);Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev.Therapeutic Drug Carrier Systems 10:307-307-377 (1993).)

[0460] Polynucleotide and Polypeptide Fragments

[0461] In the presented invention, a “polynucleotide fragment” refers toa short polynucleotide having a nucleic acid sequence contained in thedeposited clone or shown in SEQ ID NO:X. The short nucleotide fragmentsare preferably at least about 15 nt, and more preferably at least about20 nt, still more preferably at least about 30 nt, and even morepreferably, at least about 40 nt in length. A fragment “at least 20 ntin length,” for example, is intended to include 20 or more contiguousbases from the cDNA sequence contained in the deposited clone or thenucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments areuseful as diagnostic probes and primers as discussed herein. Of course,larger fragments (e.g., 50, 150, 500, 600, 2000 nucleotides) arepreferred.

[0462] Moreover, representative examples of polynucleotide fragments ofthe invention, include, for example, fragments having a sequence fromabout nucleotide number 1-20, 51-100, 101-150, 151-200, 201-250,251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 651-700,701-750, 751-800, 800-350, 851-900, 901-950, 951-1000, 1001-1050,1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350,1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650,1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950,1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained inthe deposited clone. In this context “about” includes the particularlyrecited ranges, larger or smaller by several (5, 4, 3, 2, or 1)nucleotides, at either terminus or at both termini. Preferably, thesefragments encode a polypeptide which has biological activity. Morepreferably, these polynucleotides can be used as probes or primers asdiscussed herein.

[0463] In the present invention, a “polypeptide fragment” refers to ashort amino acid sequence contained in SEQ ID NO:Y or encoded by thecDNA contained in the deposited clone. Protein fragments may be“free-standing,” or comprised within a larger polypeptide of which thefragment forms a part or region, most preferably as a single continuousregion. Representative examples of polypeptide fragments of theinvention, include, for example, fragments from about amino acid number1-20, 21-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 tothe end of the coding region. Moreover, polypeptide fragments can beabout 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150amino acids in length. In this context “about” includes the particularlyrecited ranges, larger or smaller by several (4, 3, 2, or 1) aminoacids, at either extreme or at both extremes.

[0464] Preferred polypeptide fragments include the secreted protein aswell as the mature form. Further preferred polypeptide fragments includethe secreted protein or the mature form having a continuous series ofdeleted residues from the amino or the carboxy terminus, or both. Forexample, any number of amino acids, ranging from 1-60, can be deletedfrom the amino terminus of either the secreted polypeptide or the matureform. Similarly, any number of amino acids, ranging from 1-30, can bedeleted from the carboxy terminus of the secreted protein or matureform. Furthermore, any combination of the above amino and carboxyterminus deletions are preferred. Similarly, polynucleotide fragmentsencoding these polypeptide fragments are also preferred.

[0465] Also preferred are polypeptide and polynucleotide fragmentscharacterized by structural or functional domains, such as fragmentsthat comprise alpha-helix and alpha-helix forming regions, beta-sheetand beta-sheet-forming regions, turn and turn-forming regions, coil andcoil-forming regions, hydrophilic regions, hydrophobic regions, alphaamphipathic regions, beta amphipathic regions, flexible regions,surface-forming regions, substrate binding region, and high antigenicindex regions. Polypeptide fragments of SEQ ID NO:Y falling withinconserved domains are specifically contemplated by the presentinvention. Moreover, polynucleotide fragments encoding these domains arealso contemplated.

[0466] Other preferred fragments are biologically active fragments.Biologically active fragments are those exhibiting activity similar, butnot necessarily identical to an activity of the polypeptide of thepresent invention. The biological activity of the fragments may includean improved desired activity, or a decreased undesirable activity.

[0467] Epitopes & Antibodies

[0468] In the present invention, “epitopes” refer to polypeptidefragments having antigenic or immunogenic activity in an animal,especially in a human. A preferred embodiment of the present inventionrelates to a polypeptide fragment comprising an epitope, as well as thepolynucleotide encoding this fragment. A region of a protein molecule towhich an antibody can bind is defined as an “antigenic epitope.” Incontrast, an “immunogenic epitope ” is defined as a part of a proteinthat elicits an antibody response. (See, for instance, Geysen et al.,Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983).)

[0469] Fragments which function as epitopes may be produced by anyconventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci.USA 8:5131-5135 (1935) further described in U.S. Pat. No. 4,631,211.)

[0470] In the present invention, antigenic epitopes preferably contain asequence of at least seven, more preferably at least nine, and mostpreferably between about 15 to about 30 amino acids. Antigenic epitopesare useful to raise antibodies, including monoclonal antibodies, thatspecifically bind the epitope. (See, for instance, Wilson et al., Cell37:767-778 (1984); Sutcliffe, J. G. et al., Science 219:660-666 (1983).)

[0471] Similarly, immunogenic epitopes can be used to induce antibodiesaccording to methods well known in the art. (See, for instance,Sutcliffe et al., supra, Wilson et al., supra. Chow, M. et al., Proc.Natl. Acad. Sci. USA 82.910-914; and Bittle, F. J. et al., J. Gen.Virol. 66:2347-2354 (1985).) A preferred immunogenic epitope includesthe secreted protein. The immunogenic epitopes may be presented togetherwith a carrier protein, such as an albumin, to an animal system (such asrabbit or mouse) or, if it is long enough (at least about 25 aminoacids), without a carrier. However, immunogenic epitopes comprising asfew as 8 to 10 amino acids have beer shown to be sufficient to raiseantibodies capable of binding to, at the very least, linear epitopes ina denatured polypeptide (e.g., in Western bloting.)

[0472] As used herein, the term “antibody” (Ab) or “monoclonal antibody”(Mab) is meant to include intact molecules as well as antibody fragments(such as, for example, Fab and F(ab′)2 fragments) which are capable ofspecifically binding to protein. Fab and F(ab′)2 fragments lack the Fcfragment of intact antibody, clear more rapidly from the circulation,and may have less non-specific tissue binding than an intact antibody.(Wahi et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragmentsare preferred, as well as the products of a FAB or other immunoglobulinexpression library. Moreover, antibodies of the present inventioninclude chimeric, single chain, and humanized antibodies.

[0473] Fusion Proteins

[0474] Any polypeptide of the present invention can be used to generatefusion proteins. For example, the polypeptide of the present invention,when fused to a second protein, can be used as an antigenic tag.Antibodies raised against the polypeptide of the present invention canbe used to indirectly detect the second protein by binding to thepolypeptide. Moreover, because secreted proteins target cellularlocations based on trafficking signals, the polypeptides of the presentinvention can be used as targeting molecules once fused to otherproteins.

[0475] Examples of domains that can be fused to polypeptides of thepresent invention include not only heterologous signal sequences, butalso other heterologous functional regions. The fusion does notnecessarily need to be direct, but may occur through linker sequences.

[0476] Moreover, fusion proteins may also be engineered to improvecharacteristics of the polypeptide of the present invention. Forinstance, a region of additional amino acids, particularly charged aminoacids, may be added to the N-terminus of the polypeptide to improvestability and persistence during purification from the host cell orsubsequent handling and storage. Also, peptide moieties may be added tothe polypeptide to facilitate purification. Such regions may be removedprior to final preparation of the polypeptide. The addition of peptidemoieties to facilitate handling of polypeptides are familiar and routinetechniques in the art.

[0477] Moreover, polypeptides of the present invention, includingfragments, and specifically epitopes, can be combined with parts of theconstant domain of immunoglobulins (IgG), resulting in chimericpolypeptides. These fusion proteins facilitate purification and show anincreased half-life in vivo. One reported example describes chimericproteins consisting of the first two domains of the humanCD4-polypeptide and various domains of the constant regions of the heavyor light chains of mammalian immunoglobulins. (EP A 394,827; Trauneckeret al., Nature 331:84-86 (1988).) Fusion proteins havingdisulfide-linked dimeric structures (due to the IgG) can also be moreefficient in binding and neutralizing other molecules, than themonomeric secreted protein or protein fragment alone. (Fountoulakis etal., J. Biochem. 70:3958-3964 (1995).)

[0478] Similarly, EP-A-O 464 533 (Canadian counterpart 2045869)discloses fusion proteins comprising various portions of constant regionof immunoglobulin molecules together with another human protein or partthereof. In many cases, the Fc part in a fusion protein is beneficial intherapy and diagnosis, and thus can result in, for example, improvedpharmacokinetic properties. (EP-A 0232 262.) Alternatively, deleting theFc part after the fusion protein has been expressed, detected, andpurified, would be desired. For example, the Fc portion may hindertherapy and diagnosis if the fusion protein is used as an antigen forimmunizations. In drug discovery, for example, human proteins, such ashIL-5, have been fused with Fc portions for the purpose ofhigh-throughput screening assays to identify antagonists of hIL-5. (See,D. Bennett et al., J. Molecular Recognition 8:52-58(1995); K. Johansonet al., J. Biol. Chem. 270:9459-9471 (1995).)

[0479] Moreover, the polypeptides of the present invention can be fusedto marker sequences, such as a peptide which facilitates purification ofthe fused polypeptide. In preferred embodiments, the marker amino acidsequence is a hexa-histidine peptide, such as the tag provided in a pQEvector (QIAGEIN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311),among others, many of which are commercially available. As described inGentz et al., Proc. Natl. Acad. Scl. USA 835:321-824 (1989), forinstance, hexa-histidine provides for convenient purification of thefusion protein. Another peptide tag useful for purification, the “HA”tag corresponds to an epitope derived from the influenza hemagglutininprotein. (Wilson et al., Cell 37:767 (1984).)

[0480] Thus, any of these above fusions can be engineered using thepolynucleotides or the polypeptides of the present invention.

[0481] Vectors, Host Cells, and Protein Production

[0482] The present invention also relates to vectors containing thepolynucleotide of the present invention, host cells, and the productionof polypeptides by recombinant techniques. The vector may be, forexample, a phage, plasmid, viral, or retroviral vector. Retroviralvectors may be replication competent or replication defective. In thelatter case, viral propagation generally will occur only incomplementing host cells.

[0483] The polynucleotides may be joined to a vector containing aselectable marker for propagation in a host. Generally, a plasmid vectoris introduced in a precipitate, such as a calcium phosphate precipitate,or in a complex with a charged lipid. If the vector is a virus, it maybe packaged in vitro using an appropriate packaging cell line and thentransduced into host cells.

[0484] The polynucleotide insert should be operatively linked to anappropriate promoter, such as the phage lambda PL promoter, the E. colilac, tr, phoA and tac promoters, the SV40 early and late promoters andpromoters of retroviral LTRs, to name a few. Other suitable promoterswill be known to the skilled artisan. The expression constructs willfurther contain sites for transcription initiation, termination, and, inthe transcribed region, a ribosome binding site for translation. Thecoding portion of the transcripts expressed by the constructs willpreferably include a translation initiating codon at the beginning and atermination codon (UAA, UGA or UAG) appropriately positioned at the endof the polypeptide to be translated.

[0485] As indicated, the expression vectors will preferably include atleast one selectable marker. Such markers include dihydrofolatereductase, 418 or neomycin resistance for eukaryotic cell culture andtetracycline, kanamycin or ampicillin resistance genes for culturing inE. coli and other bacteria. Representative examples of appropriate hostsinclude, but are not limited to, bacterial cells, such as E. coli,Screpcomyces and Salmonella typhimurium cells; fungal cells, such asyeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; andplant cells. Appropriate culture mediums and conditions for theabove-described host cells are known in the art.

[0486] Among vectors preferred for use in bacteria include pQE70, pQE60and pQE-9, available from QLAGEN, Inc.; pBluescrpt vectors, Phagescriptvectors, pNH8A, pNH16a, pNH18A, pNH46A, available from ScracageneCloning Systems, Inc.: and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5available from Pharmacia Biotech, Inc. Among preferred eukaryoticvectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available fromStratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia.Other suitable vectors will be readily apparent to the skilled artisan.

[0487] Introduction of the construct into the host cell can be effectedby calcium phosphate transfection, DEAE-dextran mediated transfection,cationic lipid-mediated transfection, electroporation, transduction,infection, or other methods. Such methods are described in many standardlaboratory manuals, such as Davis et al., Basic Methods In MolecularBiology (1986). It is specifically contemplated that the polypeptides ofthe present invention may in fact be expressed by a host cell lacking arecombinant vector.

[0488] A polypeptide of this invention can be recovered and purifiedfrom recombinant cell cultures by well-known methods including ammoniumsulfate or ethanol precipitation, acid extraction, amino or cationexchange chromatography, phosphocellulose chromatography, hydrophobicinteraction chromatography, affinity chromatography, hydroxylapatitechromatography and lectin chromatography. Most preferably, highperformance liquid chromatography (“HPLC”) is employed for purification.

[0489] Polypeptides of the present invention, and preferably thesecreted form, can also be recovered from: products purified fromnatural sources, including bodily fluids, tissues and cells, whetherdirectly isolated or cultured; products of chemical syntheticprocedures; and products produced by recombinant techniques from aprokaryotic or eukaryotic host, including, for example, bacterial,yeast, higher plant, insect, and mammalian cells. Depending upon thehost employed in a recombinant production procedure, the polypeptides ofthe present invention may be glycosylated or may be non-glycosylated. Inaddition, polypeptides of the invention may also include an initialmodified methionine residue, in some cases as a result of host-mediatedprocesses. Thus, it is well known in the art that the N-terminalmethionine encoded by the translation initiation codon generally isremoved with high efficiency from any protein after translation in alleukaryotic cells. While the N-terminal methionine on most proteins alsois efficiently removed in most prokaryotes, for some proteins, thisprokaryotic removal process is inefficient, depending on the nature ofthe amino acid to which the N-terminal methionine is covalently linked.

[0490] Uses of the Polynucleotides

[0491] Each of the polynucleotides identified herein can be used innumerous ways as reagents. The following description should beconsidered exemplary and utilizes known techniques.

[0492] The polynucleotides of the present invention are useful forchromosome identification. There exists an ongoing need to identify newchromosome markers, since few chromosome marking reagents, based onactual sequence data (repeat polymorphisms), are presently available.Each polynucleotide of the present invention can be used as a chromosomemarker.

[0493] Briefly, sequences can be mapped to chromosomes by preparing PCRprimers (preferably 15-15 bp) from the sequences shown in SEQ ID NO:X.Primers call be selected using computer analysis so that primers do notspan more than one-predicted exon in the genomic DNA. These primers arethen used for PCR screening of somatic cell hybrids containingindividual human chromosomes. Only those hybrids containing the humangene corresponding to the SEQ ID NO:X will yield an amplified fragment.

[0494] Similarly, somatic hybrids provide a rapid method of PCR mappingthe polynucleotides to particular chromosomes. Three or more clones canbe assigned per day using a single thermal cycle. Moreover,sublocalization of the polynucleotides can be achieved with panels ofspecific chromosome fragments. Other gene mapping strategies that can beused include in situ hybridization, prescreening with labeledflow-sorted chromosomes, and preselection by hybridization to constructchromosome specific-cDNA libraries.

[0495] Precise chromosomal location of the polynucleotides can also beachieved using fluorescence in situ hybridization (FISH) of a metaphasechromosomal spread. This technique uses polynucleotides as short as 500or 600 bases; however, polynucleotides 2,000-4,000 bp are preferred. Fora review of this technique, see Verma et al., “Human Chromosomes: aManual of Basic Techniques,” Pergamon Press, New York (1988).

[0496] For chromosome mapping, the polynucleotides can be usedindividually (to mark a single chromosomes a single site on thatchromosome) or in panels (for marking, multiple sites and/or multiplechromosomes). Preferred polynucleotides correspond to the noncodingregions of the cDNAs because the coding sequences are more likelyconserved within gene families, thus increasing the chance of crosshybridization during chromosomal mapping.

[0497] Once a polynucleotide has been mapped to a precise chromosomallocation, the physical position of the polynucleotide can be used inlinkage analysis. Linkage analysis establishes conheritance between achromosomal location and presentation of a particular disease. (Diseasemapping data are found, for example, in V. McKusick, MendelianInheritance in Man (available on line through Johns Hopkins UniversityWelch Medical Library).) Assuming 1 megabase mapping resolution and onegene per 20 kb, a cDNA precisely localized to a chromosomal regionassociated with the disease could be one of 50-500 potential causativegenes.

[0498] Thus, once coinheritance is established, differences in thepolynucleotide and the corresponding gene between affected andunaffected individuals can be examined. First, visible structuralalterations in the chromosomes such as deletions or translocations areexamined in chromosome spreads or by PCR. If no structural alterationsexist, the presence of point mutations are ascertained. Mutationsobserved in some or all affected individuals, but not in normalindividuals, indicates that the mutation may cause the disease. However,complete sequencing of the polypeptide and the corresponding gene fromseveral normal individuals is required to distinguish the mutation froma polymorphism. If a new polymorphism is identified, this polymorphicpolypeptide can be used for further linkage analysis.

[0499] Furthermore, increased or decreased expression of the gene inaffected individuals as compared to unaffected individuals can beassessed using polynucleotides of the present invention. Any of thesealterations (altered expression, chromosomal rearrangement, or mutation)can be used as a diagnostic or prognostic marker.

[0500] In addition to the foregoing, a polynucleotide can be used tocontrol gene expression through triple helix formation or antisense DNAor RNA. Both methods rely on binding of the polynucleotide to DNA orRNA. For these techniques, preferred polynucleotides are usually 20 to40 bases in length and complementary to either the region of the geneinvolved in transcription (triple helix—see Lee et al., Nucl. Acids Res.6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al.,Science 251:1360 (1991)) or to the mRNA itself (antisense—Okano, J.Neurochem. 56:560 (1991); Oligodeoxy-nucleotides as Antisense Inhibitorsof Gene Expression, CRC Press, Boca Raton, Fla. (1988).) Triple helixformation optimally results in a shut-off of RNA transcription from DNA,while antisense RNA hybridization blocks translation of an mRNA moleculeinto polypeptide. Both techniques are effective in model systems, andthe information disclosed herein can be used to design antisense ortriple helix polynucleotides in an effort to treat disease.

[0501] Polynucleotides of the present invention are also useful in genetherapy. One goal of gene therapy is to insert a normal gene into anorganism having a defective gene, in an effort to correct the geneticdefect. The polynucleotides disclosed in the present invention offer ameans of targeting such genetic defects in a highly accurate manner.Another goal is to insert a new gene :hat was not present in the hostgenome, thereby producing a new trait in the host cell.

[0502] The polynucleotides are also useful for identifying individualsfrom minute biological samples. The United States military, for example,is considering the use of restriction fragment length polymorphism(RFLP) for identification of its personnel. In this technique, anindividual's genomic DNA is digested with one or more restrictionenzymes, and probed on a Southern blot to yield unique bands foridentifying personnel. This method does not suffer from the currentlimitations of “Dog Tags” which can be lost, switched, or stolen, makingpositive identification difficult. The polynucleotides of the presentinvent or can be used as additional DNA markers for RFLP.

[0503] The polynucleotides of the present invention can also be used asan alternative to RFLP, by determining the actual base-by-base DNAsequence of selected portions of an individual's genome. These sequencescan be used to prepare PCR primers for amplifying and isolating suchselected DNA, which can then be sequenced. Using this technique,individuals can be identified because each individual will have a uniqueset of DNA sequences. Once an unique ID database is established for anindividual, positive identification of that individual, living or dead,can be made from extremely small tissue samples.

[0504] Forensic biology also benefits from using DNA-basedidentification techniques as disclosed herein. DNA sequences taken fromvery small biological samples such as tissues, e.g., hair or skin, orbody fluids, e.g., blood, saliva, semen, etc., can be amplified usingPCR. In one prior art technique, gene sequences amplified frompolymorphic loci, such as DQa class II HLA gene, are used in forensicbiology to identify individuals. (Erlich, H., PCR Technology, Freemanand Co. (1992).) Once these specific polymorphic loci are amplified,they are digested with one or more restriction enzymes, yielding anidentifying set of bands on a Southern blot probed with DNAcorresponding to the DQa class II HLA gene. Similarly, polynucleotidesof the present invention can be used as polymorphic markers for forensicpurposes.

[0505] There is also a need for reagents capable of identifying thesource of a particular tissue. Such need arises, for example, inforensics when presented with tissue of unknown origin. Appropriatereagents can comprise, for example, DNA probes or primers specific toparticular tissue prepared from the sequences of the present invention.Panels of such reagents can identify tissue by species and/or by organtype. In a similar fashion, these reagents can be used to screen tissuecultures for contamination.

[0506] In the very least, the polynucleotides of the present inventioncan be used as molecular weight markers on Southern gels, as diagnosticprobes for the presence of a specific mRNA in a particular cell type, asa probe to “subtract-out” known sequences in the process of discoveringnovel polynucleotides, for selecting and making oligmers for attachmentto a “gene chip or other support, to raise anti-DNA antibodies using DNAimmunization techniques, and as an antigen to elicit an immune response.

[0507] Uses of the Polypeptides

[0508] Each of the polypeptides identified herein can be used innumerous ways. The following description should be considered exempiaand utilizes known techniques.

[0509] A polypeptide of the present invention can be used to assayprotein levels in a biological sample using antibody-based techniques.For example, protein expression in tissues can be studied with classicalimmunohistogical methods. (Jalkanen, M., et al., J. Cell. Biol.101:976-985 (1985); Jalkanen, M., et al., J. Cell. Biol. 105:3087-3096(1987).) Other antibody-based methods useful for detecting protein geneexpression include immunoassays such as the enzyme linked immunosorbentassay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assaylabels are known in the art and include enzyme labels, such as, glucoseoxidase, and radioisotopes, such as iodine (125I, 121I), carbon (14C),sulfur (3H), tritium (3H), Indium (112In), and technetium (99mTc), andfluorescent labels, such as fluorescein and rhodamine, and biotin.

[0510] In addition to assaying secreted protein levels in a biologicalsample, proteins can also be detected in vivo by imaging. Antibodylabels or markers for in vivo imaging of protein include thosedetectable by X-radiography, NMR or ESR. For X-radiography, suitablelabels include radioisotopes such as barium or cesium, which emitdetectable radiation but are not overtly harmful to the subject.Suitable markers for NMR and ESR include those with a detectablecharacteristic spin, such as deuterium, which may be incorporated intothe antibody by labeling of nutrients for the relevant hybridoma.

[0511] A protein-specific antibody or antibody fragment which has beenlabeled with an appropriate detectable imaging moiety, such as aradioisotope (for example, 131I, 1121n, 99mTc), a radio-opaquesubstance, or a material detectable by nuclear magnetic resonance, isintroduced (for example, parenterally, subcutaneously, orintraperitoneally) into the mammal. It will be understood in the artthat the size of the subject and the imaging system used will determinethe quantity of imaging moiety needed to produce diagnostic images. Inthe case of a radioisotope moiety, for a human subject, the quantity ofradioactivity injected will normally range from about 5 to 20millicuries of 99mTc. The labeled antibody or antibody fragment willthen preferentially accumulate at the location of cells which containthe specific protein. In vivo tumor imaging is described in S. W.Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies andTheir Fragments.” (Chapter 13 in Tumor Imaging: The RadiochemicalDetection of Cancer, S. W. Burchiel and B. X. Rhodes, eds., MassonPublishing Inc. (1982).)

[0512] Thus, the invention provides a diagnostic method of a disorder,which involves (a) assaying the expression of a polypeptide of thepresent invention n cells or body fluid of an individual; (b) comparingthe level of one expression with a standard gene expression level,whereby an increase or decrease in the assayed polypeptide geneexpression level compared to the standard expression level is indicativeof a disorder.

[0513] Moreover, polypeptides of the present invention can be used totreat disease. For example, patients can be administered a polypeptideof the present invention in an effort to replace absent or decreasedlevels of the polypeptide (e.g., insulin), to supplement absent ordecreased levels of a different polypeptide (e.g., hemoglobin S forhemoglobin B), to inhibit the activity of a polypeptide (e.g. anoncogene), to activate the activity of a polypeptide (e.g., by bindingto a receptor), to reduce the activity of a membrane bound receptor bycompeting with it for free ligand (e.g., soluble TNF receptors used inreducing inflammation), or to bring about a desired response (e.g.,blood vessel growth).

[0514] Similarly, antibodies directed to a polypeptide of the presentinvention can also be used to treat disease. For example, administrationof an antibody directed to a polypeptide of the present invention canbind and reduce overproduction of the polypeptide. Similarly,administration of an antibody can activate the polypeptide, such as bybinding to a polypeptide bound to a membrane (receptor).

[0515] At the very least, the polypeptides of the present invention canbe used as molecular weight markers on SDS-PAGE gels or on molecularsieve gel filtration columns using methods well known to those of skillin the art. Polypeptides can also be used to raise antibodies, which inturn are used to measure protein expression from a recombinant cell, asa way of assessing transformation of the host cell. Moreover, thepolypeptides of the present invention can be used to test the followingbiological activities.

[0516] Biological Activities

[0517] The polynucleotides and polypeptides of the present invention canbe used in assays to test for one or more biological activities. Ifthese polynucleotides and polypeptides do exhibit activity in aparticular assay, it is likely that these molecules may be involved inthe diseases associated with the biological activity. Thus, thepolynucleotides and polypeptides could be used to treat the associateddisease.

[0518] Immune Activity

[0519] A polypeptide or polynucleotide of the present invention may beuseful in treating deficiencies or disorders of the immune system, byactivating or inhibiting the proliferation, differentiation, ormobilization (chemotaxis) of immune cells. Immune cells develop througha process called hematopoiesis, producing myeloid (platelets, red bloodcells, aeutrophis, and macrophages) and lymphoid (B and T lymphocytes)cells from pluripotent stem cells. The etiology of these immunedeficiencies or disorders may be genetic, somatic, such as cancer orsome autoimmune disorders, acquired (e.g. by chemotherapy or toxins), orinfectious. Moreover, a polynucleotide or polypeptide of the presentinvention can be used as a marker or detector of a particular immunesystem disease or disorder.

[0520] A polynucleotide or polypeptide of the present invention may beuseful in treating or detecting deficiencies or disorders ofhematopoetic cells. A polypeptide or polynucleotide of the presentinvention could be used to increase differentiation and proliferation ofhematopoletic cells, including the pluripotent stem cells, in an effortto treat those disorders associated with a decrease in certain (or many)types hematopoetic cells. Examples of immunologic deficiency syndromesinclude, but are not limited to: blood protein disorders (e.g. agammaglobulinemia, dysgammaglobulinemia), ataxia telangiectasia, commonvariable immunodeficiency, Digeorge Syndrome, HIV infection, HTLV-BLVinfection, leukocyte adhesion deficiency syndrome, lymphopenia,phagocyte bactericidal dysfunction, severe combined immunodeficiency(SCIDs), Wilskott-Aldrich Disorder, anemia, thrombocytopenia, orhemoglobinuria.

[0521] Moreover, a polypeptide or polynucleotide of the presentinvention could also be used to modulate hemostatic (the stopping ofbleeding) or dirombolytic activity (clot formation). For example, byincreasing hemostatic or dirombolytic activity, a polynucleotide orpolypeptide of the present invention could be used to treat bloodcoagulation disorders (e.g. afibrinogenemia, factor deficiencies), bloodplatlet disorders (e.g, thrombocycopenia), or wounds resulting fromtrauma, surgery, or other causes. Alternatively, a polynucleotide orpolypeptide of the present invention that can decrease hemostatic orthrombolytic activity could be used to inhibit or dissolve clotting.These molecules could be important in the treatment of heart attacks(infarction), strokes, or scarring.

[0522] A polynucleotide or polypeptide of the present invention may alsobe useful in treating or detecting autoimmune disorders. Many autoimmunedisorders result from inappropriate recognition of self as foreignmaterial by immune cells. This inappropriate recognition results in animmune response leading to the destruction of the host tissue.Therefore, the administration of a polypeptide or polynucleotide of thepresent invention that inhibits an immune response, particularly theproliferation, differentiation, or chemotaxis of T-cells, may be aneffective therapy in preventing autoimmune disorders.

[0523] Examples of autoimmune disorders that can be treated or detectedby the present invention include, but are not limited to: Addison'sDisease, hemolyzic anemia, antiphospholipid syndrome, rheumatoidarthritis, dermatitis, allergic encephalomyetils, glomerulonepbaritis,Goodpasture's Syndrome, Graves Disease, Multiple Sclerosis MyastheniaGravis, Neuritis, Ophthalmia, Bullous Pemphigold, Pemphigus,Polyendocrinopathies, Purpura, Reiter's Disease, Stiff-Man Syndrome,Autoimmune Thyroiditis, Systemic Lupus Erythematosus, AutoimmunePulmonary Inflammation, Guillain-Barre Syndrome, insulin dependentdiabetes mellitis, and autoimmune inflammatory eye disease.

[0524] Similarly, allergic reactions and conditions, such as asthma(particularly allergic asthma) or other respiratory problems, may alsobe treated by a polypeptide or polynucleotide of the present invention.Moreover, these molecules can be used to treat anaphylaxis,hypersensitivity to an antigenic molecule, or blood groupincompatibility.

[0525] A polynucleotide or polypeptide of the present invention may alsobe used to treat and/or prevent rejection or graft-versus-host disease(GVFD). Organ rejection occurs by host immune cell destruction of thetransplanted tissue through an immune response. Similarly, an immuneresponse is also involved in GVHD, but, in this case, the foreigntransplanted immune cells destroy the host tissues. The administrationof a polypeptide or polynucleotide of the present invention thatinhibits an immune response, particularly the proliferation,differentiation, or chemotaxis of T-cells, may be an effective therapyin preventing organ rejection or GVHD.

[0526] Similarly, a polypeptide or polynucleotide of the presentinvention may also be used to modulate inflammation. For example, thepolypeptide or polynucleotide may inhibit the proliferation anddifferentiation of cells involved in an inflammatory response. Thesemolecules can be used to treat inflammatory conditions, both chronic andacute conditions, including inflammation associated with infection(e.g., septic shock sepsis, or systemic inflammatory response syndrome(SIRS)), ishemia-repercussion injury, endotoxin lethality, arthritis,complement-mediated hyperacute rejection, nephritis, cytokine orchemnokine induced lung injury, inflammatory bowel disease, Crohn'sdisease, or resulting from over production of cytokines (e.g., TNF orIL-1.)

[0527] Hyperproliferative Disorders

[0528] A polypeptide or polynucleotide can be used to treat or detecthyperproliferative disorders, including neoplasms. A polypeptide orpolynucleotide of the present invention may inhibit the proliferation ofthe disorder through director indirect interactions. Alternatively, apolypeptide or polynucleotide of the present invention may proliferateother cells which can inhibit the hyperproliferative disorder.

[0529] For example, by increasing an immune response, particularlyincreasing antigenic qualities of the hyperproliferative disorders or byproliferating, differentiating, or mobilizing T-cells,hyperproliferative disorders can be treated. This immune response may beincreased by either enhancing an existing immune response, or byinitiating a new immune response. Alternatively, decreasing an immuneresponse may also be a method of treating hyperproliferative disorders,such as a chemotherapeutic agent.

[0530] Examples of hyperproliferative disorders that can be treated ordetected by a polynucleotide or polypeptide of the present inventioninclude, but are not limited to neoplasms located in the: abdomen, bone,breast, digestive system liver, pancreas, peritoneum, endocrine glands(adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid),eye, head and neck injuries (central and peripheral), lymphatic system,pelvic, skin, soft tissue, spleen, thoracic, and urogenital.

[0531] Similarly, other hyperproliferative disorders can also be treatedor detected by a polynucleotide or polypeptide of the present invention.Examples of such hyperproliferative disorders include, but are notlimited to: hypergammaglobulinemia, lymphoproliferative disorders,paraproteinernias purpura, sarcoidosis, Sezary Syndrome, Waldenstron'sMacroglobulinemia, Gaucher's Disease, histiocytosis, and any otherhyperproliferative disease, besides neoplasia, located in an organsystem listed above.

[0532] Infectious Disease

[0533] A polypeptide or polynucleotide of the present invention can beused to treat or detect infectious agents. For example, by increasingthe immune response, particularly increasing the proliferation anddifferentiation of B and/or T cells, infectious diseases may be treated.The immune response may be increased by either enhancing an existingimmune response, or by initiating a new immune response. Alternatively,the polypeptide or polynucleotide of the present invention may alsodirectly inhibit the infectious agent, without necessarily eliciting animmune response.

[0534] Viruses are one example of an infectious agent chat can causedisease or symptoms that can be treated or detected by a polynucleotideor polypeptide of the present intention. Examples of virus, include, butare not limited to the following DNA and RNA viral families: Arbovirus,Adenoviridae, Arenaviridae, Arterivrus, Birnaviridae, Bunyaviridae,Caliciviridae, Circoviridae, Coronaviridae, Flaviviridie, Hepadnaviridae(Hepatitis), Hertesviridae (such as, Cytomegalovirus, Herpes Simplex,Herpes Zoster), Mononegaviris (e.g., Paramyxoviridae, Morbillivirus,Rhabdoviridae) Orthornyxoviridae (e.g., Influenza), Papovaviridae,Paryoviridae, Picornaviridae, Poxviridae (such as Smallpox or Vaccinia),Reovirdae (e.g., Rotavirus). Retroviridae (HTLV-I, HTLVII, Lentivirus),and Togavindae (e.g., Rubivirus). Viruses falling within these familiescan cause a variety of diseases or symptoms, including, but not limitedto: arthritis, bronchiollitis, encephalitis, eye infections (e.g.conjunctivitis, keratitis), chronic fatigue syndrome, hepatitis (A, B,C, E, Chronic Active, Delta), meningitis, opportunistic infections(e.g., AIDS), pneumonia, Burkitt's Lymphoma, chickenpox, hemorrhagicfever, Measles, Mumps, Parainfluenza, Rabies, the common cold, Polio,leukemia, Rubella, sexually transmitted diseases, skin diseases (e.g.,Kaposi's, warts), and viremia. A polypeptide or polynucleotide of thepresent invention can be used to treat or detect any of these symptomsor diseases.

[0535] Similarly, bacterial or fungal agents that can cause disease orsymptoms and that can be treated or detected by a polynucleotide orpolypeptide of the present invention include, but not limited to, thefollowing Gram-Negative and Gram-positive bacterial families and fungi:Actinomycetales (e.g,., Corynebacteriuin, Mycobacterium, Norcardia),Aspergillosis, Bacillaceae (e.g., Anthrax, Clostridiumn),Bacteroidaceae, Blastomycosis, Bordetella, Borrelia, Brucellosis,Candidiasis, Campylobacter, Coccidioidomrycosis, Cryptococcosis,Dermatocycoses, Enterobacteriaceae (Klebsiella, Salmonella, Serratia,Yersinia), Erysipelothrix, Helicobacter, Legionellosis, Leptospirosis,Listeria, Mycoplasrnatales, Nieisseriaceae (e.g. Acinetobacter,Gonorrhea, Menigococcal), Pasteurellacea Infections (e.g.,Actinobacillus, Heamophilus, Pasteurella), Pseudomonas, Rickettsiaceae,Chlamydiaceae, Syphilis, and Staphylococcal. These bacterial or fungalfamilies can cause the following diseases or symptoms, including, butnot limited to: bacteremia, endocarditus, eye infections(conjunctivitis, tuberculosis, uveitis), gingivitis, opportunisticinfections (e.g., AIDS related infections), paronychia,prosthesis-related infections, Reiter's Disease, respiratory tractinfections, such as Whooping Cough or Empyema, sepsis, Lyme Disease,Cat-Scratch Disease, Dysentery, Paratyphoid Fever, food poisoning,Typhoid, pneumonia, Gonorrhea, meningitis, Chiamydia, Syphilis,Diphtheria, Leprosy, Paratuberculosis, Tuberculosis, Lupus, Botualism,gantrene, tetanus, impetigo, Rheumatic Fever, Scarlet Fever, sexuallytransmitted diseases, skin diseases (e.g. cellulitis, dermatocycoses),toxemia, urinary tract infections, wound infections. A polypeptide orpolynucleotide of the present invention can be used to treat or detectany of these symptoms or diseases.

[0536] Moreover, parasitic agents causing disease or symptoms that canbe treated or detected by a polynucleotide or polypeptide of the presentinvention include, but not limited to, the following families:Amebiasis, Babesiosis, Coccithosis, Cryptospondiosis, Dientamoebiasis,Dourine, Ectoparasitic, Giardiasis, Helminthiasis, Leishmaniasis,Theileriasis, Toxoplasmosis, Trypanosoraiasis, and Trichomonas. Theseparasites can cause a variety of diseases or symptoms, including, butnot limited to: Scabies, Trombiculiasis, eye infections, intestinaldisease (e.g., dysentery, giardiasis), liver disease, lung disease,opportunistic infections (e.g., AIDS related), Malaria, pregnancycomplications, and toxoplasmosis. A polypeptide or polynucleotide of thepresent invention can be used to treat or detect any of these symptomsor diseases.

[0537] Preferably, treatment using a polypeptide or polynucleotide ofthe present invention could either be by administering an effectiveamount of a polypeptide to the patient, or by removing cells from thepatient, supplying the cells with a polynucleotide of the presentinvention, and returning the engineered cells to the patient (ex vivotherapy). Moreover, the polypeptide or polynucleotide of the presentinvention can be used as an antigen in a vaccine to raise an immuneresponse against infectious disease.

[0538] Regeneration

[0539] A polynucleotide or polypeptide of the present invention can beused to differentiate, proliferate, and attract cells, leading to theregeneration of tissues. (See, Science 276:59-87 (1997).) Theregeneration of tissues could be used to repair, replace, or protecttissue damaged by congenital defects, trauma (wounds, burns, incisions,or ulcers), age, disease (e.g. osteoporosis, osteoarthritis, periodontaldisease, liver failure), surgery, including cosmetic plastic surgery,fibrosis, repercussion injury, or systemic cytokine damage.

[0540] Tissues that could be regenerated using the present inventioninclude organs (e.g., pancreas, liver, intestine, kidney, skin,endothelium), muscle (smooth, skeletal or cardiac), vascular (includingvascular endothelium), nervous, hematopoietic, and skeletal (bone,cartilage, tendon, and ligament) tissue. Preferably, regeneration occurswithout or decreased scarring. Regeneration also may includeangiogenesis.

[0541] Moreover, a polynucleotide or polypeptide of the presentinvention may increase regeneration of tissues difficult to heal. Forexample, increased tendon/ligament regeneration would quicken recoverytime after damage. A polynucleotide or polypeptide of the presentinvention could also be used prophylactically in an effort to avoiddamage. Specific diseases that could be treated include of tendonitis,carpal tunnel syndrome, and other tendon or ligament defects. A furtherexample of tissue regeneration of non-healing wounds includes pressureulcers, ulcers associated with vascular insufficiency, surgical, andtraumatic wounds.

[0542] Similarly, nerve and brain tissue could also be regenerated byusing a polynucleotide or polypeptide of the present invention toproliferate and differentiate nerve cells. Diseases that could betreated using this method include central and peripheral nervous system,diseases, neuropathies, or mechanical and traumatic disorders (e.g.,spinal cord disorders, head trauma, cerebrovascular disease, andstroke). Specifically, diseases associated with peripheral nerveinjuries, peripheral neuropathy (e.g., resulting from chemotherapy orother medical therapies), localized neuropathies, and central nervoussystem diseases (e.g., Alzheimer's disease, Parkinson's disease,Huntington's disease, amyotrophic lateral sclerosis, and Shy-Dragersyndrome), could all be treated using the polynucleotide or polypeptideof the present invention.

[0543] Chemotaxis

[0544] A polynucleotide or polypeptide of the present invention may havechemotaxis activity. A chemotaxic molecule attracts or mobilizes cells(e.g. monocytes, fibroblasts, neutrophils, T-cells, mast cells,eosinophils; epithelial and/or endothelial cells) to a particular sitein the body, such as inflammation, infection, or site ofhyperproliferation. The mobilized cells can then fight off and/or healthe particular trauma or abnormality.

[0545] A polynucleotide or polypeptide of the present invention mayincrease chemotaxic activity of particular cells. These chemotacticmolecules can then be used to treat inflammation, infection,hyperproliferative disorders, or any immune system disorder byincreasing the number of cells targeted to a particular location in thebody. For example, chemotaxic molecules can be used to treat wounds andother trauma to tissues by attacking, immune cells to the injuredlocation. Chemotactic molecules of the present invention can alsoattract flbroblasts, which can be used to treat wounds.

[0546] It is also contemplated that a polynucleotide or polypeptide ofthe present invention may inhibit chemotactic activity. These moleculescould also be used to treat disorders. Thus, a polynucleotide orpolypeptide of the present invention could be used as an inhibitor ofchemotaxis.

[0547] Binding Activity

[0548] A polypeptide of the present invention may be used to screen formolecules that bind to the polypeptide or for molecules to which thepolypeptide binds. The binding of the polypeptide and the molecule mayactivate (agonist), increase, inhibit (antagonist), or decrease activityof the polypeptide or the molecule bound. Examples of such moleculesinclude antibodies, oligonucleotides, proteins (e.g, receptors),or smallmolecules.

[0549] Preferably, the molecule is closely related to the natural ligandof the polypeptide, e.g. a fragment of the ligand, or a naturalsubstrate, a ligand, a structural or functional mimetic. (See, Coliganet al., Current Protocols in Immunology 1(2):Chapter 5 (1991).)Similarly, the molecule can be closely related to the natural receptorto which the polypeptide binds, or at least, a fragment of the receptorcapable of being bound by the polypeptide (e.g., active site). In eithercase, the molecule can be rationally designed using known techniques.

[0550] Preferably, the screening for these molecules involves producingappropriate cells which express the polypeptide, either as a secretedprotein or on the cell membrane. Preferred cells include cells frommammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide(or cell membrane containing the expressed polypeptide) are thenpreferably contacted with a test compound potentially containing themolecule to observe binding, stimulation, or inhibition of activity ofeither the polypeptide or the molecule.

[0551] The assay may simply test binding of a candidate compound to thepolypeptide, wherein binding is detected by a label, or in an assayinvolving competition with a labeled competitor. Further, the assay maytest whether the candidate compound results in a signal generated bybinding to the polypeptide.

[0552] Alternatively, the assay can be carried out using cell-freepreparations, polypeptide/molecule affixed to a solid support, chemicallibraries, or natural product mixtures. The assay may also simplycomprise the steps of mixing a candidate compound with a solutioncontaining a polypeptide, measuring polypeptide/molecule activity orbinding, and comparing the polypeptide/molecule activity or binding to astandard.

[0553] Preferably, an ELISA assay can measure polypeptide level oractivity in a sample (e.g., biological sample) using a monoclonal orpolyclonal antibody. The antibody can measure polypeptide level oractivity by either binding, directly or indirectly, to the polypeptideor by competing with the polypeptide for a substrate.

[0554] All of these above assays can be used as diagnostic or prognosticmarkers. The molecules discovered using these assays can be used totreat disease or to bring about a particular result in a patient (e.g.,blood vessel growth) by activating or inhibiting thepolypeptide/molecule. Moreover, the assays can discover agents which mayinhibit or enhance the production of the polypeptide from suitablymanipulated cells or tissues.

[0555] Therefore, the invention includes a method of identifyingcompounds which bind to a polypeptide of the invention comprising thesteps of: (a) incubating a candidate binding compound with a polypeptideof the invention; and (b) determining if binding has occurred. Moreover,the invention includes a method of identifying agonists/antagonistscomprising the steps of: (a) incubating a candidate compound with apolypeptide of the invention, (b) assaying a biological activity, and(b) determining if a biological activity of the polypeptide has beenaltered.

[0556] Other Activities

[0557] A polypeptide or polynucleotide of the present invention may alsoincrease or decrease the differentiation or proliferation of embryonicstem cells, besides, as discussed above, hematopoietic lineage.

[0558] A polypeptide or polynucleotide of the present invention may alsobe used to modulate mammalian characteristics, such as body height,weight, hair color, eye color, skin, percentage of adipose tissue,pigmentation, size, and shape (e.g., cosmetic surgery). Similarly, apolypeptide or polynucleotide of the present invention may be used tomodulate mammalian metabolism affecting catabolism, anabolism,processing, utilization, and storage of energy.

[0559] A polypeptide or polynucleotide of the present invention may beused to change a mammal's mental state or physical state by influencingbiorhythms, caricadic rhythms, depression (including depressivedisorders), tendency for violence, tolerance for pain, reproductivecapabilities (preferably by Activin or Irhibin-like activity), hormonalor endocrine levels, appetite, libido, memory, stress, or othercognitive qualities.

[0560] A polypeptide or polynucleotide of the present invention may alsobe used as a food additive or preservative, such as to increase ordecrease storage capabilities, fat content, lipid, protein,carbohydrate, vitamins, minerals, cofactors or other nutritionalcomponents.

[0561] Other Preferred Embodiments

[0562] Other preferred embodiments of the claimed invention include anisolated nucleic acid molecule comprising a nucleotide sequence which isat least 95% identical to a sequence of at least about 50 contiguousnucleotides in the nucleotide sequence of SEQ ID NO:X wherein X is anyinteger as defined in Table 1.

[0563] Also preferred is a nucleic acid molecule wherein said sequenceof contiguous nucleotides is included in the nucleotide sequence of SEQID NO:X in the range of positions beginning with the nucleotide at aboutthe position of the 5′ Nucleotide of the Clone Sequence and ending withthe nucleotide at about the position of the 3′ Nucleotide of the CloneSequence as defined for SEQ ID NO:X in Table 1.

[0564] Also preferred is a nucleic acid molecule wherein said sequenceof contiguous nucleotides is included in the nucleotide sequence of SEQID NO:X in the range of positions beginning with the nucleotide at aboutthe position of the 5′ Nucleotide of the Start Codon and ending with thenucleotide at about the position of the 3′ Nucleotide of the CloneSequence as defined for SEQ ID NO:X in Table 1.

[0565] Similarly preferred is a nucleic acid molecule wherein saidsequence of contiguous nucleotides is included in the nucleotidesequence of SEQ ID NO:X in the range of positions beginning with thenucleotide at about the position of the 5′ Nucleotide of the First AminoAcid of the Signal Peptide and ending with the nucleotide at about theposition of the 3′ Nucleotide of the Clone Sequence as defined for SEQID NO:X in Table 1.

[0566] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a sequence of atleast about 150 contiguous nucleotides in the nucleotide sequence of SEQID NO:X.

[0567] Further preferred is an isolated nucleic acid molecule comprisinga nucleotide sequence which is at least 95% identical to a sequence ofat least about 500 contiguous nucleotides in the nucleotide sequence ofSEQ ID NO:X.

[0568] A further preferred embodiment is a nucleic acid moleculecomprising a nucleotide sequence which is at least 95% identical to thenucleotide sequence of SEQ ID NO:X beginning with the nucleotide atabout the position of the 5′ Nucleotide of the First Amino Acid of theSignal Peptide and ending with the nucleotide at about the position ofthe 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X inTable 1.

[0569] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to the complete nucleotide sequence of SEQ ID NO:X.

[0570] Also preferred is an isolated nucleic acid molecule whichhybridizes under stringent hybridization conditions to a nucleic acidmolecule, wherein said nucleic acid molecule which hybridizes does nothybridize under stringent hybridization conditions to a nucleic acidmolecule having a nucleotide sequence consisting of only A residues orof only T residues.

[0571] Also preferred is a composition of matter comprising a DNAmolecule which comprises a human cDNA clone identified by a cDNA CloneIdentifier in Table 1, which DNA molecule is contained in the materialdeposited with the American Type Culture Collection and given the ATCCDeposit Number shown in Table 1 for said cDNA Clone Identifier.

[0572] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a sequence of atleast 50 contiguous nucleotides in the nucleotide sequence of a humancDNA clone identified by a cDNA Clone Identifier in Table 1, which DNAmolecule is contained in the deposit given the ATCC Deposit Number shownin Table 1.

[0573] Also preferred is an isolated nucleic acid molecule, wherein saidsequence of at least 50 contiguous nucleotides is included in thenucleotide sequence of the complete open reading frame sequence encodedby said human cDNA clone.

[0574] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to sequence of atleast 150 contiguous nucleotides in the nucleotide sequence encoded bysaid human cDNA clone.

[0575] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to sequence of at least 500 contiguous nucleotides in thenucleotide sequence encoded by said human cDNA clone.

[0576] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to the complete nucleotide sequence encoded by said human cDNAclone.

[0577] A further preferred embodiment is a method for detecting in abiological sample a nucleic acid molecule comprising a nucleotidesequence which is at least 95% identical to a sequence of at least 50contiguous nucleotides in a sequence selected from the group consistingof: a nucleotide sequence of SEQ ID NO:X wherein X is any integer asdefined in Table 1; and a nucleotide sequence encoded by a human cDNAclone identified by a cDNA Clone Identifier in Table 1 and contained inthe deposit with the ATCC Deposit Number shown for said cDNA clone inTable 1; which method comprises a step of comparing a nucleotidesequence of at least one nucleic acid molecule in said sample with asequence selected from said group and determining whether the sequenceof said nucleic acid molecule in said sample is at least 95% identicalto said selected sequence.

[0578] Also preferred is the above method wherein said step of comparingsequences comprises determining the extent of nucleic acid hybridizationbetween nucleic acid molecules in said sample and a nucleic acidmolecule comprising said sequence selected from said group. Similarly,also preferred is the above method wherein said step of comparingsequences is performed by comparing the nucleotide sequence determinedfrom a nucleic acid molecule in said sample with said sequence selectedfrom said group. The nucleic acid molecules can comprise cDNA moleculesor RNA molecules.

[0579] A further preferred embodiment is a method for identifying thespecies, tissue or cell type of a biological sample which methodcomprises a step of detecting nucleic acid molecules in said sample, ifany, comprising a nucleotide sequence that is at least 95% identical toa sequence of at least 50 continuous nucleotides in a sequence selectedfrom the group consisting of: a nucleotide sequence of SEQ ID NO:Xwherein X is any integer as defined in Table 1; and a nucleotidesequence encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[0580] The method for identifying the species, tissue or cell type of abiological sample can comprise a step of detecting nucleic acidmolecules comprising a nucleotide sequence in a panel of at least twonucleotide sequences, wherein at least one sequence in said panel is atleast 95% identical to a sequence of at least 50 contiguous nucleotidesin a sequence selected from said group.

[0581] Also preferred is a method for diagnosing in a subject apathological condition associated with abnormal structure or expressionof a gene encoding a secreted protein identified in Table 1, whichmethod comprises a step of detecting in a biological sample obtainedfrom said subject nucleic acid molecules, if any, comprising anucleotide sequence that is at least 95% identical to a sequence of atleast 50 contiguous nucleotides in a sequence selected from the groupconsisting of: a nucleotide sequence of SEQ ID NO:X wherein X is anyinteger as defined in Table 1; and a nucleotide sequence encoded by ahuman cDNA clone identified by a cDNA Clone Identifier in Table 1 andcontained in the deposit with the ATCC Deposit Number shown for saidcDNA clone in Table 1.

[0582] The method for diagnosing a pathological condition can comprise astep of detecting nucleic acid molecules comprising a nucleotidesequence in a panel of at least two nucleotide sequences, wherein atleast one sequence in said panel is at least 95% identical to a sequenceof at least 50 contiguous nucleotides in a sequence selected from saidgroup.

[0583] Also preferred is a composition of matter comprising isolatednucleic acid molecules wherein the nucleotide sequences of said nucleicacid molecules comprise a panel of at least two nucleotide sequences,wherein at least one sequence in said panel is at least 95% identical toa sequence of at least 50 contiguous nucleotides in a sequence selectedfrom the group consisting of: a nucleotide sequence of SEQ ID NO:Xwherein X is any integer as defined in Table 1; and a nucleotidesequence encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1. The nucleic acid moleculescan comprise DNA molecules or RNA molecules.

[0584] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 90% identical to a sequence of at least about 10contiguous amino acids in the amino acid sequence of SEQ ID NO:Y whereinY is any integer as defined in Table 1.

[0585] Also preferred is a polypeptide, wherein said sequence ofcontiguous amino acids is included in the amino acid sequence of SEQ IDNO:Y in the range of positions beginning with the residue at about theposition of the First Amino Acid of the Secreted Portion and ending withthe residue at about the Last Amino Acid of the Open Reading Frame asset forth for SEQ ID NO:Y in Table 1.

[0586] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 30contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

[0587] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 100contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

[0588] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to the complete amino acid sequenceof SEQ ID NO:Y.

[0589] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 90% identical to a sequence of at least about 10contiguous amino acids in the complete amino acid sequence of a secretedprotein encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[0590] Also preferred is a polypeptide wherein said sequence ofcontiguous amino acids is included in the amino acid sequence of asecreted portion of the secreted protein encoded by a human cDNA cloneidentified by a cDNA Clone Identifier in Table 1 and contained in thedeposit with the ATCC Deposit Number shown for said cDNA clone in Table1.

[0591] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95%a identical to a sequence of at least about 30contiguous amino acids in the amino acid sequence of the secretedportion of the protein encoded by a human cDNA clone identified by acDNA Clone Identifier in Table 1 and contained in the deposit with theATCC Deposit Number shown for said cDNA clone in Table 1.

[0592] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 100contiguous amino acids in the amino acid sequence of the secretedportion of the protein encoded by a human cDNA clone identified by acDNA Clone Identifier in Table 1 and contained in the deposit with theATCC Deposit Number shown for said cDNA clone in Table 1.

[0593] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to the amino acid sequence of thesecreted portion of the protein encoded by a human cDNA clone identifiedby a cDNA Clone Identifier in Table 1 and contained in the deposit withthe ATCC Deposit Number shown for said cDNA clone in Table 1.

[0594] Further preferred is an isolated antibody which bindsspecifically to a polypeptide comprising an amino acid sequence that isat least 90% identical to a sequence of at least 10 contiguous aminoacids in a sequence selected from the group consisting of: an amino acidsequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1;and a complete amino acid sequence of a protein encoded by a human cDNAclone identified by a cDNA Clone Identifier in Table 1 and contained inthe deposit with the ATCC Deposit Number shown for said cDNA clone inTable 1.

[0595] Further preferred is a method for detecting in a biologicalsample a polypeptide comprising an amino acid sequence which is at least90% identical to a sequence of at least 10 contiguous amino acids in asequence selected from the group consisting of: an amino acid sequenceof SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and acomplete amino acid sequence of a protein encoded by a human cDNA cloneidentified by a cDNA Clone Identifier in Table 1 and contained in thedeposit with the ATCC Deposit Number shown for said cDNA clone in Table1; which method comprises a step of comparing an amino acid sequence ofat least one polypeptide molecule in said sample with a sequenceselected from said group and determining whether the sequence of saidpolypeptide molecule in said sample is at least 90% identical to saidsequence of at least 10 contiguous amino acids.

[0596] Also preferred is the above method wherein said step of comparingan amino acid sequence of at least one polypeptide molecule in saidsample with a sequence selected from said group comprises determiningthe extent of specific binding of polypeptides in said sample to anantibody which binds specifically to a polypeptide comprising an aminoacid sequence that is at least 90% identical to a sequence of at least10 contiguous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of aprotein encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[0597] Also preferred is the above method wherein said step of comparingsequences is performed by comparing the amino acid sequence determinedfrom a polypeptide molecule in said sample with said sequence selectedfrom said group.

[0598] Also preferred is a method for identifying the species, tissue orcell-type of a biological sample which method comprises a step ofdetecting polypeptide molecules in said sample, if any, comprising anamino acid sequence that is at least 90% identical to a sequence of atleast 10 contiguous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[0599] Also preferred is the above method for identifying the species,tissue or cell type C of a biological sample, which method comprises astep of detecting polypeptide molecules comprising an amino acidsequence in a panel of at least two amino acid sequences, wherein atleast one sequence in said panel is at least 90%7a identical to asequence of at least 10 contiguous amino acids in a sequence selectedfrom the above group.

[0600] Also preferred is a method for diagnosing in a subject apathological condition associated with abnormal structure or expressionof a gene encoding a secreted protein identified in Table 1, whichmethod comprises a step of detecting in a biological sample obtainedfrom said subject polypeptide molecules comprising an amino acidsequence in a panel of at least two amino acid sequences, wherein atleast one sequence in said panel is at least 90% identical to a sequenceof at least 10 contiguous amino acids in a sequence selected from thegroup consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y isany integer as defined in Table 1; and a complete amino acid sequence ofa secreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[0601] In any of these methods, the step of detecting said polypeptidemolecules includes using an antibody.

[0602] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a nucleotidesequence encoding a polypeptide wherein said polypeptide comprises anamino acid sequence that is at least 90% identical to a sequence of atleast 10 continuous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[0603] Also preferred is an isolated nucleic acid molecule, wherein saidnucleotide sequence encoding a polypeptide has been optimized forexpression of said polypeptide in a prokaryotic host.

[0604] Also preferred is an isolated nucleic acid molecule, wherein saidpolypeptide comprises an amino acid sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[0605] Further preferred is a method of making a recombinant vectorcomprising Acura inserting any of the above isolated nucleic acidmolecule into a vector. Also preferred is the recombinant vectorproduced by this method. Also preferred is a method of making arecombinant host cell comprising introducing the vector into a hostcell, as well as the recombinant host cell produced by this method.

[0606] Also preferred is a method of making an isolated polypeptidecomprising culturing this recombinant host cell under conditions suchthat said polypeptide is expressed and recovering said polypeptide. Alsopreferred is this method of making an isolated polypeptide, wherein saidrecombinant host cell is a eukaryotic cell and said polypeptide is asecreted portion of a human secreted protein comprising an amino acidsequence selected from the group consisting of: an amino acid sequenceof SEQ ID NO:Y beginning with the residue at the position of the FirstAmino Acid of the Secreted Portion of SEQ ID NO:Y wherein Y is aninteger set forth in Table 1 and said position of the First Amino Acidof the Secreted Portion of SEQ ID NO:Y is defined in Table 1; and anamino acid sequence of a secreted portion of a protein encoded by ahuman cDNA clone identified by a cDNA Clone Identifier in Table 1 andcontained in the deposit with the ATCC Deposit Number shown for saidcDNA clone in Table 1. The isolated polypeptide produced by this methodis also preferred.

[0607] Also preferred is a method of treatment of an individual in needof an increased level of a secreted protein activity, which methodcomprises administering to such an individual a pharmaceuticalcomposition comprising an amount of an isolated polypeptide,polynucleotide, or antibody of the claimed invention effective toincrease the level of said protein activity in said individual.

[0608] Having generally described the invention, the same will be morereadily understood by reference to the following examples, which areprovided by way of illustration and are not intended as limiting.

EXAMPLES Example 1

[0609] Isolation of a Selected cDNA Clone From the Deposited Sample

[0610] Each cDNA clone in a cited ATCC deposit is contained in a plasmidvector. Table 1 identifies the vectors used to construct the cDNAlibrary from which each clone was isolated. In many cases, the vectorused to construct the library is a phage vector from which a plasmid hasbeen excised. The table immediately below correlates the related plasmidfor each phage vector used in constructing the cDNA library. Forexample, where a particular clone is identified in Table 1 as beingisolated in the vector “Lambda Zap,” the corresponding deposited cloneis in “pBluescript.” Vector Used to Construct Library CorrespondingDeposited Plasmid Lambda Zap pBluescript (pBS) Uni-Zap XR pBluescript(pBS) Zap Express pBK lafmid BA plafmid BA pSport1 pSport1 pCMVSport 2.0pCMVSport 2.0 pCMVSport 3.0 pCMVSport 3.0 pCR ®2.1 pCR ®2.1

[0611] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636),Uni-Zap XR (U.S. Pat. Nos. 5,128,256 and 5,286,636), Zap Express (U.S.Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. etal., Nucleic Acids Res. 16:7583-7600 (1988); Alting-Mees, M. A, andShort, J. M., Nucleic Acids Res. 17:9494 (1989)) and pBK (Alting-Mees,M. A. et al., Strategies 5:58-61 (1992)) are commercially available fromStratagene Cloning Systems, Inc. 11011 N. Torrey Pines Road, La Jolla,Calif., 92037. pBS contains an ampicillin resistance gene and pBKcontains a neomycin resistance gene. Both can be transformed into E.coli strain XL-1 Blue, also available from Stratagene. pBS comes in 4forms SK+, SK−, KS+ and KS. The S and K refers to the orientation of thepolylinker to the T7 and T3 primer sequences which flank the polylinkerregion (“S” is for SacI and “K” is for KpnI which are the first sites oneach respective end of the linker). “+” or “−” refer to the orientationof the f1 origin of replication (“ori”), such that in one orientation,single stranded rescue initiated from the f1 ori generates sense strandDNA and in the other, antisense.

[0612] Vectors pSport1, pCMVSport 2.0 and pCMVSport 3.0, were obtainedfrom Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897.All Sport vectors contain an ampicillin resistance gene and may betransformed into E. coli strain DH10B, also available from LifeTechnologies. (See, for instance, Gruber, C. E., et al., Focus 15:59(1993).) Vector lafmid BA (Bento Soares, Columbia University, New York)contains an ampicillin resistance gene and can be transformed into E.coli strain L-1 Blue. Vector pCR®2. 1, which is available fromInvitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains anampicillin resistance gene and may be transformed into E. coli strainDH10B, available from Life Technologies. (See, for instance, Clark J.M., Nuc. Acids Res. 16:9677-9686 (1988) and Mead, D. et al.,Bio/Technology 9: (1991).) Preferably, a polynucleotide of the presentinvention does not comprise the phage vector sequences identified forthe particular clone in Table 1, as well as the corresponding plasmidvector sequences designated above.

[0613] The deposited material in the sample assigned the ATCC DepositNumber cited in Table 1 for any given cDNA clone also may contain one ormore additional plasmids, each comprising a cDNA clone different fromthat given clone. Thus, deposits sharing the same ATCC Deposit Numbercontain at least a plasmid for each cDNA clone identified in Table 1.Typically, each ATCC deposit sample cited in Table 1 comprises a mixtureof approximately equal amounts (by weight) of about 50 plasmid DNAs,each containing a different cDNA clone; but such a deposit sample mayinclude plasmids for more or less than 50 cDNA clones, up to about 500cDNA clones.

[0614] Two approaches can be used to isolate a particular clone from thedeposited sample of plasmid DNAs cited for that clone in Table 1. First,a plasmid is directly isolated by screening the clones using apolynucleotide probe corresponding to SEQ ID NO:X.

[0615] Particularly, a specific polynucleotide with 30-40 nucleotides issynthesized using an Applied Biosystems DNA synthesizer according to thesequence reported. The oligonucleotide is labeled, for instance, with³²P-γ-ATP using T4 polynucleotide kinase and purified according toroutine methods. (E.g., Maniatis et al., Molecular Cloning: A LaboratoryManual, Cold Spring Harbor Press, Cold Spring, N.Y. (1982).) The plasmidmixture is transformed into a suitable host, as indicated above (such asXL-1 Blue (Stratagene)) using techniques known to those of skill in theart, such as those provided by the vector supplier or in relatedpublications or patents cited above. The transformants are plated on1.5% agar plates (containing the appropriate selection agent, e.g.,ampicillin) to a density of about 150 transformants (colonies) perplate. These plates are screened using Nylon membranes according toroutine methods for bacterial colony screening (e.g., Sambrook et al.,Molecular Cloning: A Laboratory Manual, 2nd Edit., (1989), Cold SpringHarbor Laboratory Press, pages 1.93 to 1.104), or other techniques knownto those of skill in the art.

[0616] Alternatively, two primers of 17-20 nucleotides derived from bothends of the SEQ ID NO:X (i.e., within the region of SEQ ID NO:X boundedby the 5′ NT and the 3′ NT of the clone defined in Table 1) aresynthesized and used to amplify the desired cDNA using the depositedcDNA plasmid as a template. The polymerase chain reaction is carried outunder routine conditions, for instance, in 25 μl of reaction mixturewith 0.5 μg of the above cDNA template. A convenient reaction mixture is1.5-5 mM MgCl₂, 0.01% (w/v) gelatin, 20 μM each of dATP, dCTP, dGTP,dTTP, 25 pmol of each primer and 0.25 Unit of Taq polymerase. Thirtyfive cycles of PCR (denaturation at 94° C. for 1 min; annealing at 55°C. for 1 min; elongation at 72° C. for 1 min) are performed with aPerkin-Elmer Cetus automated thermal cycle. The amplified product isanalyzed by agarose gel electrophoresis and the DNA band with expectedmolecular weight is excised and purified. The PCR product is verified tobe the selected sequence by subcloning and sequencing the DNA product.

[0617] Several methods are available for the identification of the 5′ or3′ non-coding portions of a gene which may not be present in thedeposited clone. These methods include but are not limited to, filterprobing, clone enrichment using specific probes, and protocols similaror identical to 5′ and 3′ “RACE” protocols which are well known in theart. For instance, a method similar to 5′ RACE is available forgenerating the missing 5′ end of a desired full-length transcript.(Fromont-Racine et al., Nucleic Acids Res. 21(7):1683-1684 (1993).)

[0618] Briefly, a specific RNA oligonucleotide is ligated to the 5′ endsof a population of RNA presumably containing full-length gene RNAtranscripts. A primer set containing a primer specific to the ligatedRNA oligonucleotide and a primer specific to a known sequence of thegene of interest is used to PCR amplify the 5′ portion of the desiredfull-length gene. This amplified product may then be sequenced and usedto generate the full length gene.

[0619] This above method starts with total RNA isolated from the desiredsource, although poly-A+RNA can be used. The RNA preparation can then betreated with phosphatase if necessary to eliminate 5′ phosphate groupson degraded or damaged RNA which may interfere with the later RNA ligasestep. The phosphatase should then be inactivated and the RNA treatedwith tobacco acid pyrophosphatase in order to remove the cap structurepresent at the 5′ ends of messenger RNAs. This reaction leaves a 5′phosphate group at the 5′ end of the cap cleaved RNA which can then beligated to an RNA oligonucleotide using T4 RNA ligase.

[0620] This modified RNA preparation is used as a template for firststrand cDNA synthesis using a gene specific oligonucleotide. The firststrand synthesis reaction is used as a template for PCR amplification ofthe desired 5′ end using a primer specific to the ligated RNAoligonucleotide and a primer specific to the known sequence of the geneof interest. The resultant product is then sequenced and analyzed toconfirm that the 5′ end sequence belongs to the desired gene.

Example 2 Isolation of Genomic Clones Corresponding to a Polynucleotide

[0621] A human genomic P1 library (Genomic Systems, Inc.) is screened byPCR using primers selected for the cDNA sequence corresponding to SEQ IDNO:X., according to the method described in Example 1. (See also,Sambrook.)

Example 3 Tissue Distribution of Polypeptide

[0622] Tissue distribution of mRNA expression of polynucleotides of thepresent invention is determined using protocols for Northern blotanalysis, described by, among others, Sambrook et al. For example, acDNA probe produced by the method described in Example 1 is labeled withp³² using the rediprime™ DNA labeling system (Amersham Life Science),according to manufacturer's instructions. After labeling, the probe ispurified using CHROMA SPIN-100™ column (Clontech Laboratories, Inc.),according to manufacturer's protocol number PT1200-1. The purifiedlabeled probe is then used to examine various human tissues for mRNAexpression.

[0623] Multiple Tissue Northern (MTN) blots containing various humantissues (H) or human immune system tissues (IM) (Clontech) are examinedwith the labeled probe using ExpressHyb™ hybridization solution(Clontech) according to manufacturer's protocol number PT1190-1.Following hybridization and washing, the blots are mounted and exposedto film at −70° C. overnight, and the films developed according tostandard procedures.

Example 4: Chromosomal Mapping of the Polynucleotides

[0624] An oligonucleotide primer set is designed according to thesequence at the 5′ end of SEQ ID NO:X. This primer preferably spansabout 100 nucleotides. This primer set is then used in a polymerasechain reaction under the following set of conditions: 30 seconds, 95°C.; 1 minutes 56° C.; 1 minute, 70° C. This cycle is repeated 32 timesfollowed by one 5 minute cycle at 70° C. Human, mouse, and hamster DNAis used as template in addition to a somatic cell hybrid panelcontaining individual chromosomes or chromosome fragments (Bios, Inc).The reactions is analyzed on either 8% polyacrylanide gels or 3.5%agarose gels, Chromosome mapping is determined by the presence of anapproximately 100 bp PCR fragment in the particular somatic cell hybrid.

Example 5: Bacterial Expression of a Polypeptide

[0625] A polynucleotide encoding a polypeptide of the present inventionis amplified using PCR oligonucleotide primers corresponding to the 5′and 3′ ends of the DNA sequence, as outlined in Example 1, to synthesizeinsertion fragments. The primers used to amplify the cDNA insert shouldpreferably contain restriction sites, such as BaraHI and XbaI, at the 5′end of the primers in order to clone the amplified product into theexpression vector. For example, BamHI and XbaI correspond to therestriction enzyme sites on the bacterial expression vector pQE-9.(Qiagen. Inc., Chatsworth, Calif.). This plasmid vector encodesantibiotic resistance (Amp_(I)), a bacterial origin of replication(ori), an IPTG-regulatable promoter/operator (P/O), a ribosome bindingsite (RBS), a 6-histidine tag (6-His), and restriction enzyme cloningsites.

[0626] The pQE-9 vector is digested with BamHI and XbaI and theamplified fragment is ligated into the pQE-9 vector maintaining thereading frame initiated at the bacterial RBS. The ligation mixture isthen used to transform the E. coli strain M15/rep4 (Qiagen, Inc.) whichcontains multiple copies of the plasmid pREP4, which expresses the lacirepressor and also confers kanamycin resistance (Kan). Transformants areidentified by their ability to grow on LB plates andampicillin/kanamycin resistant colonies are selected. Plasmid DNA isisolated and confirmed by restriction analysis.

[0627] Clones containing the desired constructs are grown overnight(O/N) in liquid culture in LB media supplemented with both Amp (100μg/ml) and Kan (25 μg/ml). The O/N culture is used to inoculate a largeculture at a ratio of 1:100 to 1:250. The cells are grown to an opticaldensity 600 (O.D.⁶⁰⁰) of between 0.4 and 0.6. IPTG(Isopropyl-B-D-thiogalacto pyranoside) is then added to a finalconcentration of 1 mM. IPTG induces by inactivating the lacd repressor,clearing the P/O leading to increased gene expression.

[0628] Cells are grown for an extra 3 to 4 hours. Cells are thenharvested by centrifugation (20 mins at 6000×g). The cell pellet issolubilized in the chaotropic agent 6 Molar Guanidine HCl by stirringfor 3-4 hours at 4° C. The cell debris is removed by centrifugation, andthe supernatant containing the polypeptide is loaded onto anickel-nitrilo-tri-acetic acid (“Ni-NTA”) affinity resin column(available from QIAGEN, Inc., supra). Proteins with a 6×His tag bind tothe Ni-NTA resin with high affinity and can be purified in a simpleone-step procedure (for details see: The QIA expressionist (1995)QIAGEIN, Inc., supra).

[0629] Briefly, the supernatant is loaded onto the column in 6 Mguanidine-HCl, pH 8, the column is first washed with 10 volumes of 6 Mguanidine-HCl, pH 8, then washed with 10 volumes of 6 M guaoidine-HCl pH6, and finally the polypeptide is eluted with 6 IM guanidine-HCl, pH 5.

[0630] The purified protein is then renatured by dialyzing it againstphosphate-buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus200 mM NaCl. Alternatively, the protein can be successfully refoldedwhile immobilized on the Ni-NTA column. The recommended conditions areas follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl,20% glycerol, 20 mM Tris/HCl pH 7.4, containing protease inhibitors. Therenaturation should be performed over a period of 1.5 hours or more.After renaturation the proteins are eluted by the addition of 250 mMimmidazole. Immidazole is removed by a final dialyzing step against PBSor 50 mM sodium acetate pH 6 buffer plus 200 mM NaCl. The purifiedprotein is stored at 4° C. or frozen at −80° C.

[0631] In addition to the above expression vector, the present inventionfurther includes an expression vector comprising phageoperator andpromoter elements operatively linked to a polynucleotide of the presentinvention, called pHE4a. (ATCC Accession Number 209645, deposited onFeb. 25, 1998.) This vector contains: 1) a neomycinphosphotransferasegene as a selection marker, 2) an E. coli origin of replication, 3) a T5phage promoter sequence, 4) two lac operator sequences, 5) aShine-Delgarno sequence, and 6) the lactose operon repressor gene(lacIq). The origin of replication (oriC) is derived from pUlC19 (LTI,Gaithersburg,, Md.). The promoter sequence and operator sequences aremade synthetically.

[0632] DNA can be inserted into the pHEa by restricting the vector withNdeI and XbaI, BamiHI, XhoI, or Asp718, running the restricted producton a gel, and isolating the larger fragment (the stuffer fragment shouldbe about 310 base pairs). The DNA insert is generated according to thePCR protocol described in Example 1, using PCR primers havingrestriction sites for NdeI (5′ primer) and XbaI, BamHI, XhoI, or Asp718(3′ primer). The PCR insert is gel purified and restricted withcompatible enzymes. The insert and vector are ligated according tostandard protocols.

[0633] The engineered vector could easily be substituted in the aboveprotocol to express protein in a bacterial system.

Example 6: Purification of a Polypeptide from an Inclusion Body

[0634] The following alternative method can be used to purify apolypeptide expressed in E coli when it is present in the form ofinclusion bodies. Unless otherwise specified, all of the following stepsare conducted at 4-10° C.

[0635] Upon completion of the production phase of the E. colifermentation, the cell culture is cooled to 4-10° C. and the cellsharvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech).On the basis of the expected yield of protein per unit weight of cellpaste and the amount of purified protein required, an appropriate amountof cell paste, by weight, is suspended in a buffer solution containing100 mil Tris, 50 mM EDTA, pH 7.4. The cells are dispersed to ahomogeneous suspension using a high shear nuxer.

[0636] The cells are then lysed by passing the solution through amicrofluidizer (Microfuidics, Corp, or APV Gaulin, Inc.) twice at4000-6000 psi. The homogenate is then mixed with NaCl solution to afinal concentration of 0.5 M NaCl, followed by centrifugation at 7000 xgfor 15 min. The resultant pellet is washed again using 0.5M NaCl, 100 mMTris, 50 mM EDTA, pH 7.4.

[0637] The resulting washed inclusion bodies are solubilized with 1.5 Mguanidine hydrochloride (GuHCl) for 2-4 hours. After 7000 xgcentrifugation for 15 min., the pellet is discarded and the polypeptidecontaining supernatant is incubated at 4° C. overnight to allow furtherGuHCl extraction.

[0638] Following high speed centrifugation (30,000 xg) to removeinsoluble particles, the GuHCl solubilized protein is refolded byquickly mixing the GuHCl extract with 20 volumes of buffer containing 50mM sodium, pH 4.5, 150 NaCl, 2 mM EDTA by vigorous stirring. Therefolded diluted protein solution is kept at 4° C. without mixing for 12hours prior to further purification steps.

[0639] To clarify the refolded polypeptide solution, a previouslyprepared tangential filtration unit equipped with 0.16 μm membranefilter with appropriate surface area (e.g., Filtron), equilibrated with40 mM sodium acetate, pH 6.0 is employed. The filtered sample is loadedonto a cation exchange resin (e.g., Poros HS-50, Perseptive Biosystems).The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with250 mM, 500 mM, 1000 mM, and 1500 mM NaCl in the same buffer, in astepwise manner. The absorbance at 280 nm of the effluent iscontinuously monitored. Fractions are collected and further analyzed bySDS-PAGE.

[0640] Fractions containing the polypeptide are then pooled and mixedwith 4 volumes of water. The diluted sample is then loaded onto apreviously prepared set of tandem columns of strong amino (Poros HQ-50,Perseptive Biosystems) and weak amino (Poros CM-20, PerseptiveBiosystems) exchange resins. The columns are equilibrated with 40 mMsodium acetate, pH 6.0. Both columns are washed with 40 mM sodiumacetate, pH 6.0, 200 mM NaCl. The CM-20 column is then eluted using a 10column volume linear gradient ranging from 0.2 M NaCl, 50 naCl sodiumacetate, pH 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5. Fractionsare collected under constant A₁₈₀ monitoring of the effluent. Fractionscontaining the polypeptide (determined, for instance, by 16% SDS-PAGE)are then pooled.

[0641] The resultant polypeptide should exhibit greater than 95% purityafter the above refolding and purification steps. No major contaminantbands should be observed from Commassie blue stained 16% SDS-PAGE gelwhen 5 μg, of purified protein is loaded. The purified protein can alsobe tested for endotoxin/LPS contamination, and typically the LPS contentis less than 0.1 ng/ml according to LAL assays.

Example 7 Cloning and Expression of a Polypeptide in a BaculovirusExpression System

[0642] In this example, the plasmid shuttle vector pA2 is used to inserta polynucleotide into a baculovirus to express a polypeptide. Thisexpression vector contains the strong polyhedrin promoter of theAutographa california nuclear polyhedrosis virus (AcNINPV) followed byconvenient restriction sites such as BarmH, Xba I and Asp718. Thepolyadenylation site of the simian virus 40 (“SV40”) is used forefficient polyadenylation. For easy selection of recombinant virus, theplasmid contains the beta-galactosidase gene from E. coli under controlof a weak Drosophila promoter in the same orientation, followed by thepolyadenylation signal of the polyhedrin gene. The inserted genes areflanked on both sides by viral sequences for cell-mediated homologousrecombination with wild-type viral DNA to generate a viable virus thatexpress the cloned polynucleotide.

[0643] Many other baculovirus vectors can be used in place of the vectorabove, such as pAc373, pVL941, and pAcIMI, as one skilled in the artwould readily appreciate, as long as the construct providesappropriately located signals for transcription, translation, secretionand the like, including a signal peptide and an in-frame AUG asrequired. Such vectors are described, for instance, in Luckow et al.,Virology 170:31-39 (1989).

[0644] Specifically, the cDNA sequence contained in the deposited clone,including the AUG initiation codon and the naturally associated leadersequence identified in Table 1, is amplified using the PCR protocoldescribed in Example 1. If the naturally occurring signal sequence isused to produce the secreted protein, the pA2 vector does not need asecond signal peptide. Alternatively, the vector can be modified (pA2GP) to include a baculovirus leader sequence, using the standard methodsdescribed in Summers et al., “A manual of Methods for BaculovirusVectors and Insect Cell Culture Procedures,” Texas AgriculturalExperimental Station Bulletin No. 1555 (1987).

[0645] The amplified fragment is isolated from a 1% agarose gel using acommercially available kit (“Geneclean,” BIO 101 Inc., La Jolla,Calif.). The fragment then is digested with appropriate restrictionenzymes and again purified on a 1% agarose gel.

[0646] The plasmid is digested with the corresponding restrictionenzymes and optionally, can be dephosphorylated using calf intestinephosphatase, using routine procedures known in the art. The DNA is thenisolated from a 1% agarose gel using a commercially available kit(“Geneclean” BIO 101 Inc., La Jolla, Calif.).

[0647] The fragment and the dephosphorylated plasmid are ligatedtogether with T4 DNA ligase. E. coli HB 101 or other suitable E. colihosts such as XL-I Blue (Stratagene Cloning Systems, La Jolla, Calif.)cells are transformed with the ligation mixture and spread on cultureplates. Bacteria containing the plasmid are identified by digesting DNAfrom individual colonies and analyzing the digestion product by gelelectrophoresis. The sequence of the cloned fragment is confirmed by DNAsequencing.

[0648] Five μg of a plasmid containing the polynucleotide isco-transfected with 1.0 μg of a commercially available linearizedbaculovirus DNA (“BaculoGold™ baculovirus DNA”, Phamungen, San Diego,Calif.), using the lipofection method described by Felgner et al., Proc.Natl. Acad. Sci. USA 84:7413-7417 (1987). One μg of BaculoGoId™ virusDNA and 5 μg of the plasmid are mixed in a sterile well of a microtiterplate containing 50 μl of serum-free Grace's medium (Life TechnologiesInc., Gaithersburg, Md.). Afterwards, 10,μl Lipofectin plus 90 μlGrace's medium are added, mixed and incubated for 15 minutes at roomtemperature. Then the transfection mixture is added drop-wise to Sf9insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with1 ml Grace's medium without serum. The plate is then incubated for 5hours at 27° C. The transfection solution is then removed from the plateand 1 ml of Grace's insect medium supplemented with 10% fetal calf serumis added. Cultivation is then continued at 27° C. for four days.

[0649] After four days the supernatant is collected and a plaque assayis performed, as described by Summers and Smith, Slapra. An agarose gelwith “Blue Gal” (Life Technologies Inc., Gaithersburg) is used to alloweasy identification and isolation of gal-expressing, clones, whichproduce blue-stained plaques. (A detailed description of a “plaqueassay” of this type can also be found in the user's guide for insectcell culture and baculovirology distributed by Life Technologies Inc.,Gaithersburg, page 9-10.) After appropriate incubation, blue stainedplaques are picked with the tip of a micropipettor (e.g., Eppendorf).The agar containing the recombinant viruses is then resuspended in amicrocentrifuge tube containing 200 μl of Grace's medium and thesuspension containing the recombinant baculovirus is used to infect Sf9cells seeded in 35 mm dishes. Four days later the supernatants of theseculture dishes are harvested and then they are stored at 4° C.

[0650] To verify the expression of the polypeptide, Sf9 cells are grownin Grace's medium supplemented with 10% heat-inactivated FBS. The cellsare infected with the recombinant baculovirus containing thepolynucleotide at a multiplicity of infection (“MIOI”) of about 2. Ifradiolabeled proteins are desired, 6 hours later the medium is removedand is replaced with SF900 II medium minus methionine and cysteine(available from Life Technologies Inc., Rockville, Md.). After 42 hours,5 μCi of ³⁵S-methionine and 5 μCi ³⁵S-cysteine (available fromArmersham) are added. The cells are further incubated for 16 hours andthen are harvested by centrifugation. The proteins in the supernatant aswell as the intracellular proteins are analyzed by SDS-PAGE followed byautoradiography (if radiolabeled).

[0651] Microsequencing of the amino acid sequence of the amino terminusof purified protein may be used to determine the amino terminal sequenceof the produced protein.

Example 8: Expression of a Polypeptide in Mammalian Cells

[0652] The polypeptide of the present invention can be expressed in amammalian cell. A typical mammalian expression vector contains apromoter element, which mediates the initiation of transcription ofmRNA, a protein coding sequence, and signals required for thetermination of transcription and polyadenylation of the transcript.Additional elements include enhancers. Kozak sequences and interveningsequences flanked by donor and acceptor sites for RNA splicing. Highlyefficient transcription is achieved with the early and late promotersfrom SV40, the long terminal repeats (LTRs) from Retroviruses, e.g.,RSV, HTLVI, HIVI and the early promoter of the cytomegalovirus (CMV).However, cellular elements can also be used (e.g., the human actinpromoter).

[0653] Suitable expression vectors for use in practicing the presentinvention include, for example, vectors such as pSVL and pMSG(Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2dhfr (ATCC37146), pBC12MI (ATCC 67109), pCMVSport 2.0, and pCMVSport 3.0.Mammalian host cells that could be used include, human Hela, 293, H9 andJurkat cells, mouse MIH3T3 and C127 cells, Cos 1, Cos 7 and CV1, quailQC1-3 cells, mouse L cells and Chinese hamster ovary (CHO) cells.

[0654] Alternatively, the polypeptide can be expressed in stable celllines containing the polynucleotide integrated into a chromosome. Theco-transfection with a selectable marker such as dhfr, gpt, neomycin,hyromycin allows the identification and isolation of the transfectedcells.

[0655] The transfected gene can also be amplified to express largeamounts of the encoded protein. The DHER (dihydrofolate reductase)marker is useful in developing cell lines that carry several hundred oreven several thousand copies of the gene of interest. (See, e.g., Alt,F. W., et al., J. Biol, Chem. 253:1357-1370 (1978); Hamlin, J. L, andMa, C., Biochem. et Biophys. Acta, 1097:107-143 (1990); Page, M. J, andSydenham, M. A., Biotechnology 9:64-68 (1991).) Another useful selectionmarker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J.227:277-279 (1991); Bebbington et al., Bio/Technology 10:169-175 (1992).Using these markers, the mammalian cells are grown in selective mediumand the cells with the nighest resistance are selected. These cell linescontain the amplified gene(s) integrated into a chromosome, Chinesehamster ovary (CHO) and NSO cells are often used for the production ofproteins.

[0656] Derivatives of the plasmid pSV2-dhfr (ATCC Accession No. 37146),the expression vectors pC4 (ATCC Accession No. 209646) and pC6 (ATCCAccession No. 209647) contain the strong promoter (LTR) of the RousSarcoma Virus (Cullen et al., Molecular and Cellular Biology, 438-447(March, 1985)) plus a fragment of the CMV-enhancer (Boshart et al., Cell41:521-530 (1985).) Multiple cloning sites, e.g., with the restrictionenzyme cleavage sites BamHII, XbaI and Asp718, facilitate the cloning ofthe gene of interest. The vectors also contain the 3′ intron, thepolyadenylation and termination signal of the rat preproinsulin gene,and the mouse DHFR gene under control of the SV40 early promoter.

[0657] Specifically, the plasmid pC6, for example, is digested withappropriate restriction enzymes and then dephosphorylated using calfintestine phosphates by procedures known in the art. The vector is thenisolated from a 1% agarose gel.

[0658] A polynucleotide of the present invention is amplified accordingto the protocol outlined in Example 1. If the naturally occurring signalsequence is used to produce the secreted protein, the vector does notneed a second signal peptide. Alternatively, if the naturally occurringsignal sequence is not used, the vector can be modified to include aheterologous signal sequence. (See, e.g., WO 96/34891.)

[0659] The amplified fragment is isolated from a 1% agarose gel using acommercially available kit (“Geneclean,” BIO 101 Inc., La Jolla,Calif.). The fragment then is digested with appropriate restrictionenzymes and again purified on a 1% agarose gel.

[0660] The amplified fragment is then digested with the same restrictionenzyme and purified on a 1% agarose gel. The isolated fragment and thedephosphorylated vector are then ligated with T4 DNA ligase. E. coli KB101 or XL-1 Blue cells are then transformed and bacteria are identifiedthat contain the fragment inserted into plasmid pC6 using, for instance,restriction enzyme analysis.

[0661] Chinese hamster ovary cells lacking an active DEFR gene is usedfor transfection. Five of the expression plasmid pC6 is cotransfectedwith 0.5 μg of the plasmid pSVneo using lipofectin (Felgner et al.,supra). The plasmid pSV2-neo contains a dominant selectable marker, theneo gene from Tn5 encoding an enzyme that confers resistance to a groupof antibiotics including G418. The cells are seeded in alpha minus MEMsupplemented with 1 mg/mi G418. After 2 days, the cells are trypsinizedand seeded in hybridoma cloning plates (Greiner, Germany) in alpha minusMEM supplemented with 10, 25, or 50 ng/ml of metothiexate plus 1 mg,/mG418. After about 10-14 days single clones are trypsinized and thenseeded in 6-well petri dishes or 10 ml flasks using differentconcentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM, 800 nM).Clones growing at the highest concentrations of methotrexate are thentransferred to new 6-well plates containing even higher concentrationsof methotrexate (1 μM, 2 μM, 5 μM, 10 nM, 20 nM). The same procedure isrepeated until clones are obtained which grow at a concentration of100-200 μM. Expression of the desired gene product is analyzed, forinstance, by SDS-PAGE and Western blot or by reversed phase HPLCanalysis.

Example 9: Protein Fusions

[0662] The polypeptides of the present invention are preferably fused toother proteins. These fusion proteins can be used for a variety ofapplications. For example, fusion of the present polypeptides toHis-tag, HA-tag, protein A, IgG domains, and maltose binding proteinfacilitates purification. (See Example 5; see also EP A 394,827;Traunecker, et al., Nature 331:84-86 (1988).) Similarly, fusion toIgG-1, IG-3, and albumin increases the half-life time in vivo. Nuclearlocalization signals fused to the polypeptides of the present inventioncan target the protein to a specific subcellular localization, whilecovalent heterodimer or homodimers can increase or decrease the activityof a fusion protein. Fusion proteins can also create chimeric moleculeshaving more than one function. Finally, fusion proteins can increasesolubility and/or stability of the fused protein compared to thenon-fused protein. All of the types of fusion proteins described abovecan be made by modifying the following protocol, which outlines thefusion of a polypeptide to an IgG molecule, or the protocol described inExample 5.

[0663] Briefly, the human Fc portion of the IgG molecule can be PCRamplified, using primers that span the 5′ and 3′ ends of the sequencedescribed below. These primers also should have convenient restrictionenzyme sites that will facilitate cloning into an expression vector,preferably a mammalian expression vector.

[0664] For example, if pC4 (Accession No. 209646) is used, the human Fcportion can be ligated into the BamHI cloning site. Note that the 3′BanHI site should be destroyed. Next, the vector containing the human Fcportion is re-restricted with BamHI, linearizing the vector, and apolynucleotide of the present invention, isolated by the PCR protocoldescribed in Example 1, is ligated into this BamHI site. Note that thepolynucleotide is cloned without a stop codon, otherwise a fusionprotein will not be produced.

[0665] If the naturally occurring signal sequence is used to produce thesecreted protein, pC4 does not need a second signal peptide.Alternatively, if the naturally occurring signal sequence is not used,the vector can be modified to include a heterologous signal sequence.(See, e.g., WO 96134891.) Human IgG Fc region:GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACACATGCCCACCGTGCC (SEQ ID NO:1)CAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGGTGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGCGACTCTAGAGGAT

Example 10 Production of an Antibody from a Polypeptide

[0666] The antibodies of the present invention can be prepared by avariety of methods. (See, Current Protocols, Chapter 2.) For example,cells expressing a polypeptide of the present invention is administeredto an animal to induce the production of sera containing polyclonalantibodies. In a preferred method, a preparation of the secreted proteinis prepared and purified to render it substantially free of naturalcontaminants. Such a preparation is then introduced into an animal inorder to produce polyclonal antisera of greater specific activity.

[0667] In the most preferred method the antibodies of the presentinvention are monoclonal antibodies (or protein binding fragmentsthereof). Such monoclonal antibodies can be prepared using hybridomatechnology. (Kohier et al., Nature 256:495 (1975) Köhler et al., Eur. J.Immunol. 6:511 (1976); Köhler et al., Eur. J. Immunol. 6:292 ( 1976);Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas,Elsevier, New York, pp. 563-681 (1981).) In general, such proceduresinvolve immunizing an animal (preferably a mouse) with polypeptide or,more preferably, with a secreted polypeptide-expressing cell. Such cellsmay be cultured in any suitable tissue culture medium; however, it ispreferable to culture cells in Earle's modified Eagle's mediumsupplemented with 10% fetal bovine serum (inactivated at about 56° C.),and supplemented with about 10 g/l of nonessential amino acids, about1,000 U/mi of penicillin, and about 100 μg/ml of streptomycin.

[0668] The splenocytes of such mice are extracted and fused with asuitable myeloma cell line. Any suitable myeloma cell line may beemployed in accordance with the present invention; however, it ispreferable to employ the parent myeloma cell line (SP2O), available fromthe ATCC. After fusion, the resulting hybridoma cells are selectivelymaintained in HAT medium, and then cloned by limiting dilution asdescribed by Wands et al. (Gastroenterology 80:2252-32 (1981).) Thehybridoma cells obtained through such a selection are then assayed toidentify clones which secrete antibodies capable of binding thepolypeptide.

[0669] Alteratively, additional antibodies capable of binding to thepolypeptide can be produced in a two-step procedure using anti-idiotypicantibodies. Such a method makes use of the fact that antibodies arethemselves antigens, and therefore, it is possible to obtain an antibodywhich binds to a second antibody. In accordance with this method,protein specific antibodies are used to immunize an animal, preferably amouse. The splenocytes of such an animal are then used to producehybridoma cells, and the hybridoma cells are screened to identify cloneswhich produce an antibody whose ability to bind to the protein-specificantibody can be blocked by the polypeptide. Such antibodies compriseanti-idiotypic antibodies to the protein-specific antibody and can beused to immunize an animal to induce formation of furtherprotein-specific antibodies.

[0670] It will be appreciated that Fab and F(ab′)2 and other fragmentsof the antibodies of the present invention may be used according to themethods disclosed herein. Such fragments are typically produced byproteolytic cleavage, using enzymes such as papain (to produce Fabfragments) or pepsin (to produce F(ab′)2 fragments). Alternatively,secreted protein-binding fragments can be produced through theapplication of recombinant DNA technology or through syntheticchemistry.

[0671] For in vivo use of antibodies in humans, it may be preferable touse “humanized” chimeric monoclonal antibodies. Such antibodies can beproduced using genetic constructs derived from hybridoma cells producingthe monoclonal antibodies described above. Methods for producingchimeric antibodies are known in the art. (See, for review, Morrison,Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Cabillyet al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrisonet al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO8702671; Boulianne et al., Nature 312:643 (1984); Neuberger et al.,Nature 314:268 (1985).)

Example 11 Production Of Secreted Protein For High-Throughput ScreeningAssays

[0672] The following protocol produces a supernatant containing apolypeptide to be tested. This supernatant can then be used in theScreening Assays described in Examples 13-20.

[0673] First, dilute Poly-D-Lysine (644 587 Boehringer-Mannheim) stocksolution (1 mg/ml in PBS) 1:20 in PBS (w/o calcium or magnesium 17-516FBiowhittaker) for a working solution of 5 μg/ml. Add 200 μl of thissolution to each well (24 well plates) and incubate at RT for 20minutes. Be sure to distribute the solution over each well (note: a12-channel pipetter may be used with tips on every other channel).Aspirate off the Poly-D-Lysine solution and rinse with 1 ml PBS(Phosphate Buffered Saline). The PBS should remain in the well untiljust prior to plating the cells and plates may be poly-lysine coated inadvance for up to two weeks.

[0674] Plate 293T cells (do not carry cells past P+20) at 2×10⁵cells/well in 0.5 ml DMEM (Dulbeccol's Modified Eagle Medium) (with 4.5G/L glucose and L-glutamine (12-604F Biowhittaker))/10% heat inactivatedFBS(14-503F Biowhittaker)/1×Penstrep(17-602E Biowhittaker). Let thecells grow overnight.

[0675] The next day, mix together in a sterile solution basin: 300 μlLipofectamine (18324-012 Gibco/BRL) and 5 ml Optimem I (31985070Gibco/BRL)/96-well plate. With a small volume multi-channel pipetter,aliquot approximately 2μg of an expression vector containing apolynucleotide insert, produced by the methods described in Examples 8or 9, into an appropriately labeled 96-well round bottom plate. With amulti-channel pipetter, add 50μl of the Lipofectamine/Optimem I mixtureto each well. Pipette up and down gently to mix. Incubate at RT 15-45minutes. After about 20 minutes, use a multi-channel pipetter to add 150μl Optimem I to each well. As a control, one plate of vector DNA lackingan insert should be transfected with each set of transfections.

[0676] Preferably, the transfection should be performed by tag-teamingthe following tasks. By tag-teaming, hands on time is cut in half, andthe cells do not spend too much time on PBS. First, person A aspiratesoff the media from four 24-well plates of cells, and then person Brinses each well with 0.5-1 ml PBS. Person A then aspirates off PBSrinse, and person B, using a12-channel pipetter with tips on every otherchannel, adds the 200 μl of DNA/Lipofectamiine/Optimem I complex to theodd wells first, then to the even wells, to each row on the 24-wellplates. Incubate at 37° C. for 6 hours.

[0677] While cells are incubating, prepare appropriate media, either 1%BSA in DNEM with 1×penstrep, or CHO-5 media (116.6 mg/L of CaC12(anhyd); 0.00130 mg/L CuSO₄-5H₂O; 0.050 mg/L of Fe(NO₃)3 -9HO; 0.417mg/L of FeSO₄-7H₂O; 311.80 mg/L of Kcl; 28.64 mg/L of MgCl1; 48.84 mg/Lof MgSO₄; 6995.50 mg/L of NaCl; 2400.0 mg/L of NaHCO₃; 62.50 mg/L ofNaH₂PO₄-H₂O; 71.02 mg/L of Na₂HPO₄; 0.4320 mg/L of ZnSO₄-7H₂O; 0.002mg/L of Arachidonic Acid; 1.02-2 mg/L of Cholesterol;.070 mg/L ofDL-alpha-Tocopherol-Acetate; 0.0520 mg/L of Linoleic Acid; 0.010 mg/L ofLinolenic Acid; 0.010 mg/L of Myrstic Acid; 0.010 mg/L of Oleic Acid;0.010 mg/L of Palmitric Acid; 0.010 mg/L of Palmitic Acid; 100 mg/L ofPluronic F-68; 0.010 mg/L of Stearic Acid; 2.20 mg/L of Tween 80; 4551mg/L of D-Glucose; 130.85 mg/ml of L- Alanine; 147.50 mg/ml ofL-Arginine-HCL; 7.50 mg/ml of L-Asparagine-H₂O; 6.65 mg/1 ml ofL-Aspartic Acid; 29.56 mg/ml of L-Cystine-2HCL-H₂O; 31.29 mg/ml ofL-Cystine-2HCL; 7.35 mg/ml of L-Glutamic Acid; 365.0 mg/ml ofL-Glutamine; 18.75 mg/ml of Glycine; 52.48 mg/ml of L-Histidine-HCL-H₂O;106.97 mg/ml of L-Isoleucine; 111.45 mg/ml of L-Leucine; 163.75 mg/ml ofL-Lysine HCL; 32.34 mg/ml of L-Methionine; 68.48 mg/ml ofL-Phenylalainine; 40.0 mg/ml of L-Proline; 26.25 mg/ml of L-Serine;101.05 mg/ml of L-Threonine; 19.22 mg/ml of L-Tryptophan; 91.79 mg/ml ofL-Tryrosine-2Na-2H₂O; 99.65 mg/ml of L-Valine; 0.0035 mg/L of Biotin;3.24 mg/L of D-Ca Pantothenate; 11.78 mg/L of Choline Chloride; 4.65mg/L of Folic Acid; 15.60 mg/L of 1-Inositol; 3.02 mg/L of Niacinamide;3.00 mg/L of Pyridoxal HCL; 0.031 mg/L of Pyridoxine HCL; 0.319 mg/L ofRiboflavin; 3.17 mg/L of Thiamine HCL; 0.365 mg/L of Thymidine; and0.680 mg/L of Vitarmin B₁₂; 25 mM of HEPES Buffer; 2.39 mg/L of NaHypoxanthine; 0.105 mg/L of Lipoic Acid; 0.081 mg/L of SodiumPutrescine-2HCL; 55.0 mg/L of Sodium Pyruvate; 0.0067 mg/l of SodiumSelenite; 20 μM of Ethanolamine; 0.122 mg/L of Ferric Citrate; 41.70mg/L of Methyl-B-Cyclodextrin complexed with Linoleic Acid; 33.33 mg/lof Methyl-B-Cyclodextrin complexed with Oleic Acid; and 10 mg/L ofMethyl-B-Cyclodextrin complexed with Retinal) with 2 mm glutamine and1×penstrep. (BSA (81-068-3 Bayer) 100 gm dissolved in IL DMEM for a 10%BSA stock solution). Filter the media and collect 50 μl for endotoxinassay in 15 ml polystyrene conical.

[0678] The transfection reaction is terminated, preferably bytag-teaming, at the end of the incubation period. Person A aspirates offthe transfection media, while person B adds 1.5 ml appropriate media toeach well. Incubate at 37° C. for 45 or 72 hours depending on the mediaused. 1% BSA for 45 hours or CHO-5 for 72 hours.

[0679] On day four, using a 300 μl multichannel pipetter, aliquot 600 μlin one 1 ml deep well plate and the remaining supernatant into a 2 mldeep well. The supernatants from each well can then be used in theassays described in Examples 13-20.

[0680] It is specifically understood that when activity is obtained inany of the assays described below using a supernatant, the activityoriginates from either the polypeptide directly (e.g., as a secretedprotein) or by the polypeptide inducing expression of other proteins,which are then secreted into the supernatant. Thus, the inventionfurther provides a method of identifying the protein in the supernatantcharacterized by an activity in a particular assay.

Example 12 Construction of GAS Reporter Construct

[0681] One signal transduction pathway involved in the differentiationand proliferation of cells is called the Jaks-STATs pathway. Activatedproteins in the Jaks-STATs pathway bind to gamma activation site “GAS”elements or interferon-sensitive responsive element (“ISRE”), located inthe promoter of many genes. The binding of a protein to these elementsalter the expression of the associated gene.

[0682] GAS and ISRE elements are recognized by a class of transcriptionfactors called Signal Transducers and Activators of Transcription, or“STATs.” There are six members of the STATs family. Stat1 and Stat3 arepresent in many cell types, as is Stat2 (as response to IFN-alpha iswidespread). Stat4 is more restricted and is not in many cell typesthough it has been found in T helper class I, cells after treatment withIL-12. Stat5 was originally called mammary growth factor, but has beenfound at higher concentrations in other cells including myeloid cells.It can be activated in tissue culture cells by many cytokines.

[0683] The STATs are activated to translocate from the cytoplasm to thenucleus upon tyrosine phosphorylation by a set of kinases known as theJanus Kinase (⁴Jaks”) family. Jaks represent a distinct family ofsoluble frosine lanases and include Tyk2, Jak1, Jak2, and Jak3. Thesekinases display significant sequence similarity and are generallycatalytically inactive in resting cells.

[0684] The Jaks are activated by a wide range of receptors summarized inthe Table below. (Adapted from review by Schidler and Darnell, Ann. Rev.Biochem. 64:621-51 (1995).) A cytokine receptor family, capable ofactivating Jaks, is divided into two groups: (a) Class 1 includesreceptors for IL-2, IL-3, TL-4, L-6, IL-7, IL-9, IL-11, IL-12, IL-15,Epo, PRL, GH, G-CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and (b)Class 2 includes IFN-a, IFN-g, and IL-10. The Class 1 receptors share aconserved cysteine motif (a set of four conserved cysteines and onetryptophan) and a WSXWS motif (a membrane proxial region encodingTrp-Ser-Xxx-Trp-Ser (SEQ ID NO:2)).

[0685] Thus, on binding of a ligand to a receptor, Jaks are activated,which in turn activate STATs, which then translocate and bind to GASelements. This entire process is encompassed in the Jaks-STATs signaltransduction pathway.

[0686] Therefore, activation of the Jaks-STATs pathway, reflected by thebinding of the GAS or the ISRE element, can be used to indicate proteinsinvolved in the proliferation and differentiation of cells. For example,growth factors and cytokines are known to activate the Jaks-STATspathway. (See Table below.) Thus, by using GAS elements linked toreporter molecules, activators of the Jaks-STATs pathway can beidentified. JAKs Ligand tyk2 Jak1 Jak2 Jak3 STATS GAS (elements) or ISREIFN-family IFN-a/B + + − − 1, 2, 3 ISRE IFN-g + + − 1 GAS(IRF1>Lys6>IFP) Il-10 + ? ? − 1, 3 gp130 family IL-6 (Pleiotrohic) + + +? 1, 3 GAS (IRF1>Lys6>IFP) Il-11 (Pleiotrohic) ? + ? ? 1, 3 OnM(Pleiotrohic) ? + + ? 1, 3 LIF (Pleiotrohic) ? + + ? 1, 3 CNTF(Pleiotrohic) −/+ + + ? 1, 3 G-CSF (Pleiotrohic) ? + ? ? 1, 3 IL-12(Pleiotrohic) + − + + 1, 3 g-C family IL-2 (lymphocytes) − + − + 1, 3, 5GAS IL-4 (lymph/myeloid) − + − + 6 GAS (IRF1 = IFP >>Ly6)(IgH) IL-7(lymphocytes) − + − + 5 GAS IL-9 (lymphocytes) − + − + 5 GAS IL-13(lymphocyte) − + ? ? 6 GAS IL-15 ? + ? + 5 GAS gp140 family IL-3(myeloid) − − + − 5 GAS (IRF1>IFP>>Ly6) IL-5 (myeloid) − − + − 5 GASGM-CSF (myeloid) − − + − 5 GAS Growth hormone family GH ? − + − 5 PRL ?+/− + − 1, 3, 5 EPO ? − + − 5 GAS (B−CAS>IRF1=IFP>>Ly6) ReceptorTyrosine Kinases EGF ? + + − 1, 3 GAS (IRF1) PDGF ? + + − 1, 3 CSF-1? + + − 1, 3 GAS (not IRF1)

[0687] To construct a synthetic GAS containing promoter element, whichis used in the Biological Assays described in Examples 13-14, a PCRbased strategy is employed to generate a GAS-SV40 promoter sequence. The5′ primer contains four tandem copies of the GAS binding site found inthe IRFI promoter and previously demonstrated to bind STATs uponinduction with a range of cytokines (Rothman et al., Immunity 1:457-468(1994).), although other GAS or ISRE elements can be used instead. The5′ primer also contains 18 bp of sequence complementary to the SV40early promoter sequence and is flanked with an XhoI site. The sequenceof the 5′ primer is:5′:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCG (SEQ ID NO:3)AAATGATTTCCCCGAAATATCTGCCATCTCAATTAG:3′

[0688] The downstream primer is complementary to the 5V40 promoter andis flanked with a Hind mI site: 5:GCGGCAAGCTTTTTGCAAiGCCTAGGC:3′ (SEQ IDNO:4)

[0689] PCR amplification is performed using the SV40 promoter templatepresent in the B-gal:promoter plasmid obtained from Clontech. Theresulting PCR fragment is digested with XhoI/Hind HI and subcloned intoBLSK2—. (Stratagene.) Sequencing with forward and reverse primersconfirms that the insert contains the following sequence:5′:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATG (SEQ ID NO:5)ATTTCCCCGAAATATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTT TGCAAAAAGCTT:3′

[0690] With this GAS promoter element linked to the SV40 promoter, aGAS:SEAP2 reporter construct is next engineered. Here, the reportermolecule is a secreted alkaline phosphatase, or “SEAP.” Clearly,however, any reporter molecule can be instead of SEAP, in this or in anyof the other Examples. Well known reporter molecules that can be usedinstead of SEAP include chloramphenicol acetyltransferase (CAT),luciferase, alkaline phosphatase, B-galactosidase, green fluorescentprotein (GFP), or any protein detectable by an antibody.

[0691] The above sequence confirmed synthetic GAS-SV40 promoter elementis subcloned into the pSEA.P-Promoter vector obtained from Clontechusing HindIII and XhoI, effectively replacing the SV40 promoter with theamplified GAS:SV40 promoter element, to create the GAS-SEAP vector.However, this vector does not contain a neomycin resistance gene, andtherefore, is not preferred for mammalian expression systems.

[0692] Thus, in order to generate mammalian stable cell lines expressingthe GAS-SEAP reporter, the GAS-SEAP cassette is removed from theGAS-SEAP vector using SalI and NotI, and inserted into a backbone vectorcontaining the neomycin resistance gene, such as pGEFP-1 (Clontech),using these restriction sites in the multiple cloning site, to createthe GAS-SEAP/Neo vector. Once this vector is transfected into mammaliancells, this vector can then be used as a reporter molecule for GASbinding as described in Examples 13-14.

[0693] Other constructs can be made using the above description andreplacing GAS with a different promoter sequence. For example,construction of reporter molecules containing NFK-B and EGR promotersequences are described in Examples 15 and 16. However, many otherpromoters can be substituted using the protocols described in theseExamples. For instance, SRE, TL-2, NFAT, or Osteocalcin promoters can besubstituted, alone or in combination (e.g., GASINF-KB/EGR, GAS/NF-KB,Il-2/NFAT, or NF-KB/GAS). Similarly, other cell lines can be used totest reporter construct activity, such as HELA (epithelial), HUVEC(endothelial), Reh (B-cell), Saos-2 (osteoblast), HUVAC (aortic), orCardiomyocyte.

Example 13 High-Throughput Screening Assay for T-cell Activity

[0694] The following protocol is used to assess T-cell activity byidentifying factors, such as growth factors and cytokines, that mayproliferate or differentiate T-cells. T-cell activity is assessed usingthe GAS/SEAP/Neo construct produced in Example 12. Thus, factors thatincrease SEAP activity indicate the ability to activate the Jaks-STATSsignal transduction pathway. The T-cell used in this assay is JurkatT-cells (ATCC Accession No. TIB-152), although Molt-3 cells (ATCCAccession No, CRL-1552) and Molt-4 cells (ATCC Accession No, CRL-1582)cells can also be used.

[0695] Jurkat T-cells are lymphoblastic CD4+ Th1 helper cells. In orderto generate stable cell lines, approximately 2 million Jurkat cells aretransfected with the GAS-SEAP/neo vector using DMRIE-C (LifeTechnologies) (transfection procedure described below). The transfectedcells are seeded to a density of approximately 20,000 cells per well andtransfectants resistant to 1 mg/ml genticin selected. Resistant coloniesare expanded and then tested for their response to increasingconcentrations of interferon gamma. The dose response of a selectedclone is demonstrated.

[0696] Specifically, the following protocol will yield sufficient cellsfor 75 wells containing 200 μl of cells. Thus, it is either scaled up,or performed in multiple to generate sufficient cells for multiple 96well plates. Jurkat cells are maintained in RPNI+10% senim with 1%Pen-Strep, Combine 2.5 mls of OPTI-MEM (Life Technologies) with 10 μg ofplasmid DNA in a T25 flask. Add 2.5 ml OPTI-MEM containing 50 μl ofDMRIE-C and incubate at room temperature for 15-45 mins.

[0697] During the incubation period, count cell concentration, spin downthe required number of cells (10⁷ per transfection), and resuspend inOPTI-MEM to a final concentration of 10⁷ cells/ml. Then add 1 ml of1×10⁷ cells in OPIIE™ to T25 flask and incubate at 37° C. for 6 hrs.After the incubation, add 10 ml of RPNU + 15% serum.

[0698] The Jurkat:GAS-SEAP stable reporter lines are maintained inRPMI+10% serum, 1 mg/ml Genticin, and 1% Pen-Strep. These cells aretreated with supernatants containing a polypeptide as produced by theprotocol described in Example 11.

[0699] On the day of treatment with the supernatant, the cells should bewashed and resuspended in fresh RPMI+ 10% serum to a density of 500,000cells per ml. The exact number of cells required will depend on thenumber of supernatants being screened. For one 96 well plate,approximately 10 million- cells (for 10 plates, 100 million cells) arerequired.

[0700] Transfer the cells to a triangular reservoir boat, in order todispense the cells into a 96 well dish, using a 12 channel pipette.Using a 12 channel pipette, transfer 200 μl of cells into each well(therefore adding 100,000 cells per well).

[0701] After all the plates have been seeded, 50 μl of the supernatantsare transferred directly from the 96 well plate containing thesupernatants into each well using a 12 channel pipette. In addition, adose of exogenous interferon gamma (0.1, 1.0, 10 ng) is added to wellsH9, H10, and H11 to serve as additional positive controls for the assay.

[0702] The 96 well dishes containing Jurkat cells treated withsupernatants are placed in an incubator for 48 hrs (note: this time isvariable between 48-72 hrs). 35 μl samples from each well are thentransferred to an opaque 96 well plate using a 12 channel pipette. Theopaque plates should be covered (using sellophene covers) and stored at−20° C. until SEAP assays are performed according to Example 17. Theplates containing the remaining treated cells are placed at 40C andserve as a source of material for repeating the assay on a specific wellif desired.

[0703] As a positive control, 100 Unit/ml interferon gamma can be usedwhich is known to activate Jurkat T cells. Over 30 fold induction istypically observed in the positive control wells.

Example 14 High-Throughput Screening Assay Identifying Myeloid Activity

[0704] The following protocol is used to assess myeloid activity byidentifying factors, such as growth factors and cytokines, that mayproliferate or differentiate myeloid cells. lyeloid cell activity isassessed using the GAS/SEAP/Neo construct produced in Example 12. Thus,factors that increase SEAP activity indicate the ability to activate theJaks-STATS signal transduction pathway. The myeloid cell used in thisassay is U937, a pre-monocyte cell line, although TF-1, HL60, or KGI canbe used.

[0705] To transiently transfect U937 cells with the GAS/SEP/Neoconstruct produced in Example 12, a DEAE-Dextran method (Kharbanda et.al., 1994, Cell Growth & Differentiation, 5:259-265) is used. First,harvest 2×10e⁷ U937 cells and wash with PBS. The U937 cells are usuallygrown in RPMI 1640 medium containing10% heat-inactivated fetal bovineserum (FBS) supplemented with 100 units/ml penicillin and 100 mg/mlstreptomycin.

[0706] Next, suspend the cells in 1 ml of 20 mM Tris-HCl (pH 7.4) buffercontaining 0.5 mg/ml DEAE-Dextran, 8 μg GAS-SEAP2 plasmid DNA, 140 mMNaCl, 5 mM KCl, 375 μM Na₂HPO₄.7H₂O, 1 mM MgCl₂, and 675 μM CaCl₂.Incubate at 37° C. for 45 min.

[0707] Wash the cells with RPMI 1640 medium containing 10% FBS and thenresuspend in 10 ml complete medium and incubate at 37° C. for 36 hr.

[0708] The GAS-SEAP/U937 stable cells are obtained by growing the cellsin 400 μg/ml G418. The G418-free medium is used for routine growth butevery one to two months, the cells should be re-grown in 400 μgl/ml G418for couple of passages.

[0709] These cells are tested by harvesting 1×10⁸ cells (this is enoughfor ten 96-well plates assay) and wash with PBS. Suspend the cells in200 ml above described growth medium, with a final density of5×10-cells/ml. Plate 200 μl cells per well in the 96-well plate (or1×10⁵ cells/well).

[0710] Add 50 μl of the supernatant prepared by the protocol describedin Example 11. Incubate at 37° C. for 48 to 72 hr. As a positivecontrol, 100 unit/ml interferon gamma can be used which is known toactivate U937 cells. Over 30 fold induction is typically observed in thepositive control wells. SEAP assay the supernatant according to theprotocol described in Example 17.

Example 15 High-Throughput Screening Assay Identifying NeuronalActivity.

[0711] When cells undergo differentiation and proliferation, a group ofgenes are activated through many different signal transduction pathways.One of these genes, EGR1 (early growth response gene 1), is induced invarious tissues and cell types upon activation. The promoter of EGR1 isresponsible for such induction. Using the EGR1 promoter linked toreporter molecules, activation of cells can be assessed.

[0712] Particularly, the following protocol is used to assess neuronalactivity in PC12 cell lines. PC12 cells (rat phenochromocytoma cells)are known to proliferate and/or differentiate by activation with anumber of ml togens, such as TPA (tetradecanoyl phorbol acetate), NGF(nerve growth factor), and EGF (epidermal growth factor). The EGR1 geneexpression is activated during this treatment. Thus, by stablytransfecting PC12 cells with a construct containing an EOR promoterlinked to SEAP reporter, activation of PC12 cells can be assessed.

[0713] The EGR/SEAP reporter construct can be assembled by the followingprotocol. The EGR-1 promoter sequence (−633 to +1) (Sakaamoto K et al.,Oncogene 6:867-371 (1991)) can be PCR amplified from human genomic DNAusing the following primers: 5′ GCGCTCGAGGGATGACAGCGATAGAACCCCGG-3′ (SEQID NO:6) 5′ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3′ (SEQ ID NO:7)

[0714] Using the GAS:SEAP/Neo vector produced in Example 12, EGR1amplified product can then be inserted into this vector. Linearize theGAS:SEAP/Neo vector using restriction enzymes XhoI/HindIII, removing theGAS/SV40 stuffer. Restrict the EGR1 amplified product with these sameenzymes. Ligate the vector and the EGR1 promoter.

[0715] To prepare 96 well-plates for cell culture, two mls of a coatingsolution (1:30 dilution of collagen type I (Upstate Biotech Inc,Cat#08-115) in 30% ethanol (filter sterilized)) is added per one 10 cmplate or 50 ml per well of the 96-well plate, and allowed to air dry for2 hr.

[0716] PC12 cells are routinely grown in RPMI-1640 medium (BioWhittaker) containing 10% horse serum (JRH BIOSCIENCES, Cat. #12449-78P), 5% heat-inactivated fetal bovine serum (FBS) supplementedwith 100 unitslml penicillin and 100 μg/ml streptomycin on a precoated10 cm tissue culture dish. One to four split is done every three to fourdays, Cells are removed from the plates by scraping and resuspended withpipetting up and down for more than 15 times.

[0717] Transfect the EGR/SEAP/Neo construct into PC12 using theLipofectamine protocol described in Example 11. EGR-SEAP PC12 stablecells are obtained by growing the cells in 300 μg/ml G418. The G418-freemedium is used for routine growth but every one to two months, the cellsshould be re-grown in 300 μμg/ml G418 for couple of passages.

[0718] To assay for neuronal activity, a 10 cm plate with cells around70 to 80% confluent is screened by removing the old medium. Wash thecells once with PBS (Phosphate buffered saline). Then starve the cellsin low serum medium (RPMI-1640 containing 1% horse serum and 0.5% FBSwith antibiotics) overnight.

[0719] The next morning, remove the medium and wash the cells with PBS.Scrape off the cells from the plate, suspend the cells well in 2 ml lowserum medium, Count the cell number and add more low serum medium toreach final cell density as 5×10⁵ cells/ml.

[0720] Add 200 μl of the cell suspension to each well of 96-well plate(equivalent to 1×10⁵ cells/well). Add 50 μl supernatant produced byExample I 1, 37° C. for 48 to 72 hr. As a positive control, a growthfactor known to activate PC 12 cells through EGR can be used, such as 50ng/μl of Neuronal Growth Factor (NGF). Over fifty-fold induction of SEAPis typically seen in the positive control wells. SEAP assay thesupernatant according to Example 17.

Example 16: High-Throughput Screening Assay for T-cell Activity

[0721] NF-κB (Nuclear Factor κB) is a transcription factor activated bya wide variety of agents including the inflammatory cytokines IL-1 andTNF, CD30 and CD40, lymphotoxin-alpha and lymphotoxin-beta, by exposureto LPS or thrombin, and by expression of certain viral gene products. Asa transcription factor, NF-κB regulates the expression of genes involvedin immune cell activation, control of apoptosis (NB-κB appears to shieldcells from apoptosis), B and T-cell development, anti-viral andantimicrobial responses, and multiple stress responses.

[0722] In non-stimulated conditions, NF-κB is retained in the cytoplasmwith I-κB (Inhibitor κB). However, upon stimulation, I-κB isphosphorylated and degraded, causing NF-κB to shuttle to the nucleus,thereby activating transcription of target genes. Target genes activatedby NF-κB include IL-2, L-6, GM-CSF, ICAM-1 and class 1 MHC.

[0723] Due to its central role and ability to respond to a range ofstimuli, reporter constructs utilizing the NF-κB promoter element areused to screen the supernatants produced in Example 11. Activators orinhibitors of NF-κB would be useful in treating diseases. For example,inhibitors of NF-κB could be used to treat those diseases related to theacute or chronic activation of NF-κB, such as rheumatoid arthritis.

[0724] To construct a vector containing the NF-κB promoter element, aPCR based strategy is employed. The upstream primer contains four tandemcopies of the NF-κB binding site (GGGGACTTTCCC) (SEQ ID NO:8), 18 bp ofsequence complementary to the 5′ end of the SV40 early promotersequence, and is flanked with an XhoI site:5′:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGAC (SEQ ID NO:9)TTTCCATCCTGCCATCTCAATTAG:3′

[0725] The downstream primer is complementary to the 3′ end of the SV40promoter and is flanked with a Hind III site:

[0726] 5:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3(SEQ ID NO:4)

[0727] PCR amplification is performed using the SV40 promoter templatepresent in the pB-gal:promoter plasmid obtained from Clontech. Theresulting PCR fragment is digested with Xhol and Hind II and subclonedinto BLSK2—. (Stratagene) Sequencing with the T7 and T3 primers confirmsthe insert contains the following sequence:5′:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTT (SEQ ID NO:10)CCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGC AAAAAGCTT:3′

[0728] Next, replace the SV40 minimal promoter element present in thepSEAP2-promoter plasmid (Clontech) with this NF-κB/SV40 fragment usingXhoI and HindIII. However, this vector does not contain a neomycinresistance gene, and therefore, is not preferred for mammalianexpression systems.

[0729] In order to generate stable mammalian cell lines, theNF-κB/SV40/SEAP cassette is removed from the above NF-κB/SEAP vectorusing restriction enzymes SaII and NotI, and inserted into a vectorcontaining neomycin resistance. Particularly, the NF-κB/SV40/SEAPcassette was inserted into pGFP-1 (Clontech), replacing the GFP gene,after restricting pGFP-1 with Sall and Notl.

[0730] Once NF-κB/SV40/SEAP/Neo vector is created, stable Jurkat T-cellsare created and maintained according to the protocol described inExample 13. Similarly, the method for assaying supernatants with thesestable Jurkat T-cells is also described Example 13. As a positivecontrol, exogenous TNF alpha (0.1,1, 10 ng) is added to wells H9, H10,and H11, with a 5-10 fold activation typically observed.

Example 17 Assay for SEAP Activity

[0731] As a reporter molecule for the assays described in Examples13-16, SEAP activity is assayed using the Tropix Phospho-light Kit (Cat.BP400) according to the following general procedure. The TropixPhospho-light Kit supplies the Dilution, Assay, and Reaction Buffersused below.

[0732] Prime a dispenser with the 2.5× Dilution Buffer and dispense 15μl of 2.5×dilution buffer into Optiplates containing 35 μl of asupernatant. Seal the plates with a plastic sealer and incubate at 65°C. for 30 min. Separate the Optiplates to avoid uneven heating.

[0733] Cool the samples to room temperature for 15 minutes. Empty thedispenser and prime with the Assay Buffer. Add 50 μl Assay Buffer andincubate at room temperature 5 min. Empty the dispenser and prime withthe Reaction Buffer (see the table below). Add 50 μl Reaction Buffer andincubate at room temperature for 20 minutes. Since the intensity of thechemiluminescent signal is time dependent, and it takes about 10 minutesto read 5 plates on luminometer, one should treat 5 plates at each timeand start the second set 10 minutes later.

[0734] Read the relative light unit in the luminometer. Set H12 as blankand print the results. An increase in chemiluminescent indicatesreporter activity. Reaction Buffer Formulation: # of plates Rxn bufferdiluent (ml) CSPD (ml) 10 60 3 11 65 3.25 12 70 3.5 13 75 3.75 14 80 415 85 4.25 16 90 4.5 17 95 4.75 18 100 5 19 105 5.25 20 110 5.5 21 1155.75 22 120 6 23 125 6.25 24 130 6.5 25 135 6.75 26 140 7 27 145 7.25 28150 7.5 29 155 7.75 30 160 8 31 165 8.25 32 170 8.5 33 175 8.75 34 180 935 185 9.25 36 190 9.5 37 195 9.75 38 200 10 39 205 10.25 40 210 10.5 41215 10.75 42 220 11 43 225 11.25 44 230 11.5 45 235 11.75 46 240 12 47245 12.25 48 250 12.5 49 255 12.75 50 260 13

Example 18 High-Throughput Screening Assay Identifying Chances in SmallMolecule Concentration and Membrane Permeability

[0735] Binding of a ligand to a receptor is known to alter intracellularlevels of small molecules, such as calcium, potassium, sodium, and pH,as well as alter membrane potential. These alterations can be measuredin an assay to identify supernatants which bind to receptors of aparticular cell. Although the following protocol describes an assay forcalcium, this protocol can easily be modified to detect changes inpotassium, sodium, pH, membrane potential, or any other small moleculewhich is detectable by a fluorescent probe.

[0736] The following assay uses Fluorometric Imaging Plate Reader(“FLIPR”) to measure changes in fluorescent molecules (Molecular Probes)that bind small molecules, Clearly, any fluorescent molecule detecting asmall molecule can be used instead of the calcium fluorescent molecule,fluo-3, used here.

[0737] For adherent cells, seed the cells at 10,000-20,000 cells/well ina Co-star black 96-well plate with clear bottom. The plate is incubatedin a CO₂ incubator for 20 hours. The adherent cells are washed two timesin Biotek washer with 200 μl of HBSS Hank's Balanced Salt Solution)leaving 100 μl of buffer after the final wash.

[0738] A stock solution of 1 mg/ml fluo-3 is made in 10% pluronic acidDMSO. To load the cells with fluo-3, 50 μl of 12 μg/ml fluo-3 is addedto each well. The plate is incubated at 37° C. in a CO₂ incubator for 60min. The plate is washed four times in the Biotek washer with HBSSleaving 100 μl of buffer.

[0739] For non-adherent cells, the cells are spun down from culturemedia, Cells are re-suspended to 2×10⁶ cells/ml with HBSS in a 50-mlconical tube. 4 μl of 1 mg/ml fluo-3 solution in 10% pluronic acid DMSOis added to each ml of cell suspension. The tube is then placed in a 37°C. water bath for 30-60 min. The cells are washed twice with HBSS,resuspended to 1×10⁶ cells/ml, and dispensed into a microplate, 100μl/well. The plate is centrifuged at 1000 rpm for 5 min. The plate isthen washed once in Denley CellWash with 200 μl, followed by anaspiration step to 100 μl final volume.

[0740] For a non-cell based assay, each well contains a fluorescentmolecule, such as fluo-3. The supernatant is added to the well, and achange in fluorescence is detected.

[0741] To measure the fluorescence of intracellular calcium, the FLIPRis set for the following parameters: (1) System gain is 300-800 mW; (2)Exposure time is 0.4 second; (3) Camera F/stop is F/2; (4) Excitation is488 nm; (5) Emission is 530 nm; and (6) Sample addition is 50 μl.Increased emission at 530 nm indicates an extracellular signaling eventwhich has resulted in an increase in the intracellular Ca⁺⁺concentration.

Example 19 High-Throughput Screening Assay Identifying Tyrosine KinaseActivity

[0742] The Protein Tyrosine Kinases (PTK) represent a diverse group oftransmembrane and cytoplasmic kinases. Within the Receptor ProteinTyrosine Kinase RPTK) group are receptors for a range of mitogenic andmetabolic growth factors including the PDGF, FGF, EGF, NGF, HGF andInsulin receptor subfamilies. In addition there are a large family ofRPTKs for which the corresponding ligand is unknown. Ligands for RPTKsinclude mainly secreted small proteins, but also membrane-bound andextracellular matrix proteins.

[0743] Activation of RPTK by ligands involves ligand-mediated receptordimerization, resulting in transphosphorylation of the receptor subunitsand activation of the cytoplasmic tyrosine kinases. The cytoplasmictyrosine kinases include receptor associated tyrosine kinases of thesrc-family (e.g., src, yes, lck lyn, fyn) and non-receptor linked andcytosolic protein tyrosine kinases, such as the Jak family, members ofwhich mediate signal transduction triggered by the cytokine superfamilyof receptors (e.g., the Interleukins, Interferons, GM-CSF, and Leptin).

[0744] Because of the wide range of known factors capable of stimulatingtyrosine kinase activity, the identification of novel human secretedproteins capable of activating tyrosine kinase signal transductionpathways are of interest. Therefore, the following protocol is designedto identify those novel human secreted proteins capable of activatingthe tyrosine kinase signal transduction pathways.

[0745] Seed target cells (e.g., primary keratinocytes) at a density ofapproximately 25,000 cells per well in a 96 well Loprodyne Silent ScreenPlates purchased from Nalge Nunc (Naperville, Ill.). The plates aresterilized with two 30 minute rinses with 100% ethanol, rinsed withwater and dried overnight. Some plates are coated for 2 hr with 100 mlof cell culture grade type I collagen (50 mg/ml), gelatin (2%o) orpolylysine (50 mg/mi), all of which can be purchased from SigmaChemicals (St. Louis, Mo.) or 10% Matrigel purchased from BectonDickinson (Bedford, Mass.), or calf serum, rinsed with PBS and stored at4° C., Cell growth on these plates is assayed by seeding 5,000cells/well in growth medium and indirect quantitation of cell numberthrough use of alamarBlue as described by the manufacturer AlamarBiosciences, Inc. (Sacramento, Calif.) after 48 hr. Falcon plate covers#3071 from Becton Dickinson (Bedford, Mass.) are used to cover theLoprodyne Silent Screen Plates. Falcon Microtest III cell culture platescan also be used in some proliferation experiments.

[0746] To prepare extracts, A431 cells are seeded onto the nylonmembranes of Loprodyne plates (20,000/200 ml/well) and culturedovernight in complete medium. Cells are quiesced by incubation inserum-free basal medium for 24 hr. After 5-20 minutes treatment with EGF(60 ng/ml) or 50 μl of the supernatant produced in Example 11, themedium was removed and 100 ml of extraction buffer ((20 mM HEPES pH 7.5,0.15 M NaCl, 1% Triton X-100, 0.1% SDS, 2 mM Na3VO4, 2 nM Na4P207 and acocktail of protease inhibitors (# 1836170) obtained from BoeheringerMannheim (Indianapolis, Ind.) is added to each well and the plate isshaken on a rotating shaker for 5 minutes at 4° C. The plate is thenplaced in a vacuum transfer manifold and the extract filtered throughthe 0.45 mm membrane bottoms of each well using house vacuum. Extractsare collected in a 96-well catch/assay plate in the bottom of the vacuummanifold and immediately placed on ice. To obtain extracts clarified bycentrifugation, the content of each well, after detergent solubilizationfor 5 minutes, is removed and centrifuged for 15 minutes at 4° C. at16,000×g.

[0747] Test the filtered extracts for levels of tyrosine kinaseactivity. Although many methods of detecting tyrosine kinase activityare known, one method is described here.

[0748] Generally, the tyrosine kinase activity of a supernatant isevaluated by determining its ability to phosphorylate a tyrosine residueon a specific substrate (a biotinylated peptide). Biotinylated peptidesthat can be used for this purpose include PSKI (corresponding to aminoacids 6-20 of the cell division kinase cdc2-p34) and PSK2 (correspondingto amino acids 1-17 of gastrin). Both peptides are substrates for arange of tyrosine kinases and are available from Boehringer Mannheim.

[0749] The tyrosine kinase reaction is set up by adding the followingcomponents in order. First, add 10 μl of 5 μM Biotinylated Peptide, then10 μl ATP/Mg₂₊ (5 mM ATP/50 mM MgCl₂) then 10 μl of 5×Assay Buffer (40mM imidazole hydrochloride, pH7.3, 40 mM beta-glycerophosphate, 1 mMEGTA, 100 mM MgCl₂, 5 mM MnCl₂, 0.5 mg/ml BSA), then 5 μl of SodiumVanadate (1 mM), and then 5μl of water. Mix the components gently andpreincubate the reaction mix at 30° C. for 2 mn. Initial the reaction byadding 10 μl of the control enzyme or the filtered supernatant.

[0750] The tyrosine kinase assay reaction is then terminated by adding10 μl of 120mm EDTA and place the reactions on ice.

[0751] Tyrosine kinase activity is determined by transferring 50 μlaliquot of reaction mixture to a microtiter plate (MTP) module andincubating at 37° C. for 20 min. This allows the streptavadin coated 96well plate to associate with the biotinylated peptide. Wash the MTPmodule with 300 μl/well of PBS four times. Next add 75 μl ofanti-phospotyrosine antibody conjugated to horse radishperoxidase(anti-P-Tyr-POD(0.5 μ/ml)) to each well and incubate at 37° C.for one hour. Wash the well as above.

[0752] Next add 100 μl of peroxidase substrate solution (BoehringerMannheim) and incubate at room temperature for at least 5 mins (up to 30min). Measure the absorbance of the sample at 405 nm by using ELISAreader. The level of bound peroxidase activity is quantitated using anELISA reader and reflects the level of tyrosine kinase activity.

Example 20 High-Throughput Screening Assay Identifying PhosphorylationActivity

[0753] As a potential alternative and/or compliment to the assay ofprotein tyrosine kinase activity described in Example 19, an assay whichdetects activation (phosphorylation) of major intracellular signaltransduction intermediates can also be used. For example, as describedbelow one particular assay can detect tyrosine phosphorylation of theErk-1 and Erk-2 kinases. However, phosphorylation of other molecules,such as Raf, JNK, p38 MAP, Map kinase (MEK), MEK kinase, Src, Musclespecific kinase (MuSK), IRAK, Tec, and Janus, as well as any otherphosphoserine, phosphotyrosine, or phosphothreonine molecule, can bedetected by substituting these molecules for Erk-1 or Erk-2 in thefollowing assay.

[0754] Specifically, assay plates are made by coating the wells of a96-well ELISA plate with 0.1 ml of protein G (1 μg/mi) for 2 hr at roomtemp, (RT). The plates are then rinsed with PBS and blocked with 3%BSA/PBS for 1 hr at RT. The protein G plates are then treated with 2commercial monoclonal antibodies (100 ng/well) against Erk-1 and Erk-2(1 hr at RT) (Santa Cruz Biotechnology). (To detect other molecules,this step can easily be modified by substituting a monoclonal antibodydetecting any of the above described molecules.) After 3-5 rinses withPBS, the plates are stored at 4° C. until use.

[0755] A431 cells are seeded at 20,000/well in a 96-well Loprodynefilterplate and cultured overnight in growth medium. The cells are thenstarved for 48 hr in basal medium (DMEM) and then treated with ECF (6ng/well) or 50 μl of the supernatants obtained in Example 11 for 5-20minutes. The cells are then solubilized and extracts filtered directlyinto the assay plate.

[0756] After incubation with the extract for 1 hr at RT, the wells areagain rinsed. As a positive control, a commercial preparation of MAPkinase (10 ng/well) is used in place of A431 extract. Plates are thentreated with a commercial polyclonal (rabbit) antibody (1 μg/ml) whichspecifically recognizes the phosphorylated epitope of the Erk-1 andErk-2 kinases (1 hr at RT). This antibody is biotinylated by standardprocedures. The bound polyclonal antibody is then quantitated bysuccessive incubations with Europium-streptavidin and Europiumfluorescence enhancing reagent in the Wallac DELFIA instrument(time-resolved fluorescence). An increased fluorescent signal overbackground indicates a phosphorylation.

Example 21 Method of Determining Alterations in a Gene Corresponding toa Polynucleotide

[0757] RNA isolated from entire families or individual patientspresenting with a phenotype of interest (such as a disease) is beisolated. cDNA is then generated from these RNA samples using protocolsknown in the art. (See, Sambrook.) The cDNA is then used as a templatefor PCR, employing primers surrounding regions of interest in SEQ IDNO:X. Suggested PCR conditions consist of 35 cycles at 95° C. for 30seconds; 60-120 seconds at 52-58° C.; and 60-120 seconds at 70° C.,using buffer solutions described in Sidransky, D., et al., Science252:706 (1991).

[0758] PCR products are then sequenced using primers labeled at their 5′end with T4 polynucleotide kinase, employing SequiTherm Polymerase.(Epicentre Technologies). The intron-exon borders of selected exons isalso determined and genomic PCR products analyzed to confirm theresults. PCR products harboring suspected mutations is then cloned andsequenced to validate the results of the direct sequencing.

[0759] PCR products is cloned into T-tailed vectors as described inHolton, T. A, and Graham, M. W., Nucleic Acids Research, 19:1156 (1991)and sequenced with T7 polymerase (United States Biochemical). Affectedindividuals are identified by mutations not present in unaffectedindividuals.

[0760] Genomic rearrangements are also observed as a method ofdetermining alterations in a gene corresponding to a polynucleotide.Genomic clones isolated according to Example 2 are nick-translated withdigoxigenindeoxy-uridine 5′-triphosphate (Boehringer Manheim), and FISHperformed as described in Johnson, Cg. et al., Methods Cell Biol.35:73-99 (1991). Hybridization with the labeled probe is carried outusing a vast excess of human cot-1 DNA for specific hybridization to thecorresponding genomic locus. .Chromosomes are counterstained with4,6-diamino-2-phenylidole and propidium iodide, producing a combinationof C- and R-bands. Aligned images for precise mapping are obtained usinga triple-band filter set (Chroma Technology, Brattleboro, Vt.) incombination with a cooled charge-coupled device camera (Photometrics,Tucson, Ariz.) and variable excitation wavelength filters. (Johnson, Cv.et al., Genet. Anal. Tech. Appl., 8:75 (1991).) Image collection,analysis and chromosomal fractional length measurements are performedusing the ISee Graphical Program System. (Inovision Corporation, Durham,N.C.) Chromosome alterations of the genomic region hybridized by theprobe are identified as insertions, deletions, and translocations. Thesealterations are used as a diagnostic marker for an associated disease.

Example 22 Method of Detecting Abnormal Levels of a Polypeptide in aBiological Sample

[0761] A polypeptide of the present invention can be detected in abiological sample, and if an increased or decreased level of thepolypeptide is detected, this polypeptide is a marker for a particularphenotype. Methods of detection are numerous, and thus, it is understoodthat one skilled in the art can modify the following assay to fit theirparticular needs.

[0762] For example, antibody-sandwich ELISAs are used to detectpolypeptides in a sample, preferably a biological sample. Wells of amicrotiter plate are coated with specific antibodies, at a finalconcentration of 0.2 to 10 μg/ml. The antibodies are either monoclonalor polyclonal and are produced by the method described in Example 10.The wells are blocked so that non-specific binding of the polypeptide tothe well is reduced.

[0763] The coated wells are then incubated for >2 hours at RT with asample containing the polypeptide. Preferably, serial dilutions of thesample should be used to validate results. The plates are then washedthree times with deionized or distilled water to remove unboundedpolypeptide.

[0764] Next, 50 μl of specific antibody-alkaline phosphatase conjugate,at a concentration of 25-400 ng is added and incubated for 2 hours atroom temperature. The plates are again washed three times with deionizedor distilled water to remove unbounded conjugate.

[0765] Add 75 μl of 4-methylumbelliferyl phosphate (MUP) orp-nitrophenyl phosphate (NPP) substrate solution to each well andincubate 1 hour at room temperature. Measure the reaction by amicrotiter plate reader. Prepare a standard curve, using serialdilutions of a control sample, and plot polypeptide concentration on theX-axis (log scale) and fluorescence or absorbance of the Y-axis (linearscale). Interpolate the concentration of the polypeptide in the sampleusing the standard curve.

Example 23 Formulating a Polypeptide

[0766] The secreted polypeptide composition will be formulated and dosedin a fashion consistent with good medical practice, taking into accountthe clinical condition of the individual patient (especially the sideeffects of treatment with the secreted polypeptide alone), the site ofdelivery, the method of administration, the scheduling ofadministration, and other factors known to practitioners. The “effectiveamount” for purposes herein is thus determined by such considerations.

[0767] As a general proposition, the total pharmaceutically effectiveamount of secreted polypeptide administered parenterally per dose willbe in the range of about 1 μg/kg/day to 10 mg/kg/day of patient bodyweight, although, as noted above, this will be subject to therapeuticdiscretion. More preferably, this dose is at least 0.01 mg/kg/day, andmost preferably for humans between about 0.01 and 1 mg/kg/day for thehormone. If given continuously, the secreted polypeptide is typicallyadministered at a dose rate of about 1 μg/kg/hour to about 50μg/kg/hour, either by 1-4 injections per day or by continuoussubcutaneous infusions, for example, using a mini-pump. An intravenousbag solution may also be employed. The length of treatment needed toobserve chances and the interval following treatment for responses tooccur appears to vary depending on the desired effect.

[0768] Pharmaceutical compositions containing the secreted protein ofthe invention are administered orally, rectally, parenterally,intracistemally, intravaginally, intraperitoneaIly, topically (as bypowders, ointments, gels, drops or transdermal patch), bucally, or as anoral or nasal spray. “Pharmaceutically acceptable carrier” refers to anon-toxic solid, semisolid or liquid filler, diluent, encapsulatingmaterial or formulation auxiliary of any type. The term “parenteral” asused herein refers to modes of administration which include intravenous,intramuscular, intraperitoneal, intrasternal, subcutaneous andintraarticular injection and infusion.

[0769] The secreted polypeptide is also suitably administered bysustained-release systems. Suitable examples of sustained-releasecompositions include semi-permeable polymer matrices in the form ofshaped articles, e.g., films, or mirocapsules. Sustained-releasematrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481),copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman, U. etal., Biopolymers 22:547-556 (1983)), poly (2-hydroxyethyl methacrylate)(R. Lancer et al., J. Biomed. Mater. Res. 15:167-277 (1981), and R.Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Lanceret al.) or poly-D- (−)-3-hydroxybutyric acid (EP 133,988).Sustained-release compositions also include liposomally entrappedpolypeptides. Liposomes containing the secreted polypeptide are preparedby methods known per se: DE 3,218,121; Epstein et al., Proc. Natl. Acad.Scd. USA 82:3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA77:4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP142,641; Japanese Pat. Appl. 83-118008; U.S. Pat. Nos. 4,485,045 and4,544,545; and EP 102,324. Ordinarily, the liposomes are of the small(about 200-800 Angstroms) umlamellar type in which the lipid content isgreater than about 30 mol. percent cholesterol, the selected proportionbeing adjusted for the optimal secreted polypeptide therapy.

[0770] For parenteral administration, in one embodiment, the secretedpolypeptide is formulated generally by mixing it at the desired degreeof purity, in a unit dosage injectable form (solution, suspension, oremulsion), with a pharmaceutically acceptable carrier, i.e., one that isnontoxic to recipients at the dosages and concentrations employed and iscompatible with other ingredients of the formulation. For example, theformulation preferably does not include oxidizing agents and othercompounds that are known to be deleterious to polypeptides.

[0771] Generally, the formulations are prepared by contacting thepolypeptide uniformly and intimately with liquid carriers or finelydivided solid carriers or both. Then, if necessary, the product isshaped into the desired formulation. Preferably the carrier is aparenteral carrier, more preferably a solution that is isotonic with theblood of the recipient. Examples of such carrier vehicles include water,saline, Ringer's solution, and dextrose solution. Non-aqueous vehiclessuch as fixed oils and ethyl oleate are also useful herein, as well asliposomes.

[0772] The carrier suitably contains minor amounts of additives such assubstances that enhance isotonicity and chemical stability. Suchmaterials are non-toxic to recipients at the dosages and concentrationsemployed, and include buffers such as phosphate, citrate, suiccinate,acetic acid, and other organic acids or their salts; antioxidants suchas ascorbic acid; low molecular weight (less than about ten residues)polypeptides, e.g., polyarginine or tripeptides; proteins, such as serumalbumin, gelatin, or immunoglobulins, hydrophilic polymers such aspolyvinylpyrrolidone; amino acids, such as glycine, glutamic acid,aspartic acid, or arginine; monosaccharides, disacchandes, and othercarbohydrates including cellulose or its derivatives, glucose, manose,or dextrins; chelating agents such as EDTA; sugar alcohols such asmannitol or sorbitol; counterions such as sodium; and/or nonionicsurfactants such as polysorbates, poloxamers, or PEG.

[0773] The secreted polypeptide is typically formulated in such vehiclesat a concentration of about 0.1 mg/ml to 100 mg/ml, preferably 1-10mg/ml, at a pH of about 3 to 8. It will be understood that the use ofcertain of the foregoing excipients, carriers, or stabilizers willresult in the formation of polypeptide salts.

[0774] Any polypeptide to be used for therapeutic administration can besterile. Sterility is readily accomplished by filtration through sterilefiltration membranes (e.g., 0.2 micron membranes). Therapeuticpolypeptide compositions generally are placed into a container having asterile access port, for example, an intravenous solution bag or vialhaving a stopper pierceable by a hypodermic injection needle.

[0775] Polypeptides ordinarily will be stored in unit or multi-dosecontainers, for example, sealed ampoules or vials, as an aqueoussolution or as a lyophilized formulation for reconstitution. As anexample of a lyophilized formulation, 10-ml vials are filled with 5 mlof sterile-filtered 1% (w/v) aqueous polypeptide solution, and theresulting mixture is lyophilized. The infusion solution is prepared byreconstituting the lyophilized polypeptide using bacteriostaticWater-for-Injection.

[0776] The invention also provides a pharmaceutical pack or kitcomprising one or more containers filled with one or more of theingredients of the pharmaceutical compositions of the invention.Associated with such container(s) can be a notice in the form prescribedby a governmental agency regulating the manufacture, use or sale ofpharmaceuticals or biological products, which notice reflects approvalby the agency of manufacture, use or sale for human administration. Inaddition, the polypeptides of the present invention may be employed inconjunction with other therapeutic compounds.

Example 24 Method of Treating Decreased Levels of the Polypeptide

[0777] It will be appreciated that conditions caused by a decrease inthe standard or normal expression level of a secreted protein in anindividual can be treated by administering the polypeptide of thepresent invention, preferably in the secreted form. Thus, the inventionalso provides a method of treatment of an individual in need of anincreased level of the polypeptide comprising administering to such anindividual a pharmaceutical composition comprising an amount of thepolypeptide to increase the activity level of the polypeptide in such anindividual.

[0778] For example, a patient with decreased levels of a polypeptidereceives a daily dose 0.1-100 μg/kg of the polypeptide for sixconsecutive days. Preferably, the polypeptide is in the secreted form.The exact details of the dosing scheme, based on administration andformulation, are provided in Example 23.

Example 25 Method of Treating Increased Levels of the Polypeptide

[0779] Antisense technology is used to inhibit production of apolypeptide of the present invention. This technology is one example ofa method of decreasing levels of a polypeptide, preferably a secretedform, due to a variety of etiologies, such as cancer.

[0780] For example, a patient diagnosed with abnormally increased levelsof a polypeptide is administered intravenously antisense polynucleotidesat 0.5, 1.0, 1.5, 2.0 and 3.0 mg/kg day for 21 days. This treatment isrepeated after a 7-day rest period if the treatment was well tolerated.The formulation of the antisense polynucleotide is provided in Example23.

Example 26 Method of Treatment Using Gene Therapy

[0781] One method of gene therapy transplants fibroblasts, which arecapable of expressing a polypeptide, onto a patient. Generally,fibroblasts are obtained from a subject by skin biopsy. The resultingtissue is placed in tissue-culture medium and separated into smallpieces. Small chunks of the tissue are placed on a wet surface of atissue culture flask approximately ten pieces are placed in each flask.The flask is turned upside down, closed tight and left at roomtemperature over night. After 24 hours at room temperature, the flask isinverted and the chunks of tissue remain fixed to the bottom of theflask and fresh media (e.g., Ham's F12 media, with 10% FBS, penicillinand streptomycin) is added. The flasks are then incubated at 37° C. forapproximately one week.

[0782] At this time, fresh media is added and subsequently changed everyseveral days. After an additional two weeks in culture, a monolayer offibroblasts emerge. The monolayer is trypsinized and scaled into largerflasks.

[0783] pMV-7 (Kirschlmeier, P. T. et al., DNA, 7:219-25 (1988)), flankedby the long terminal repeats of the Moloney murine sarcoma virus, isdigested with EcoRI and HindiH and subsequently treated with calfintestine phosphatase. The linear vector is fractionated on agarose geland purified. Using glass beads.

[0784] The cDNA encoding a polypeptide of the present invention can beamplified using PCR primers which correspond to the 5′ and 3′ endsequences respectively as set forth in Example 1. Preferably, the 5′primer contains an EcoRI site and the 3′ primer includes a HindIII site.Equal quantities of the Moloney murine sarcoma virus linear backbone andthe amplified EcoRI and HindHI fragment are added together, in thepresence of T4 DNA ligase. The resulting mixture is maintained underconditions appropriate for ligation of the two fragments. The ligationmixture is then used to transform bacteria HB 101, which are then platedonto agar containing kanamycin for the purpose of confirming that thevector has the gene of interest properly inserted.

[0785] The amphotropic pA317 or GP+am12 packaging cells are grown intissue culture to confluent density in Dulbecco's Modified Eagles Medium(DMNEM) with 10% calf serum (CS), penicillin and streptomycin. The MSVvector containing the gene is then added to the media and the packagingcells transduced with the vector. The packaging cells now produceinfectious viral particles containing the gene (the packaging cells arenow referred to as producer cells).

[0786] Fresh media is added to the transduced producer cells, andsubsequently, the media is harvested from a 10 cm plate of confluentproducer cells. The spent media, containing the infectious viralparticles, is filtered through a millipore filter to remove detachedproducer cells and this media is then used to infect fibroblasts cells.Media is removed from a sub-confluent plate of fibroblasts and quicklyreplaced with the media from the producer cells. This media is removedand replaced with fresh media. If the titer of virus is high, thenvirtually all fibroblasts will be infected and no selection is required.If the titer is very low, then it is necessary to use a retrieval vectorthat has a selectable marker, such as neo or his. Once the fibroblastshave been efficiently infected, the fibroblasts are analyzed todetermine whether protein is produced.

[0787] The engineered fibroblasts are then transplanted onto the host,either alone or after having been grown to confluence on cytodex 3microcarrier beads.

[0788] It will be clear that the invention may be practiced otherwisethan as particularly described in the foregoing description andexamples. Numerous modifications and variations of the present inventionare possible in light of the above teachings and, therefore, are withinthe scope of the appended claims.

[0789] The entire disclosure of each document cited (including patents,patent applications, journal articles, abstracts, laboratory manuals,books, or other disclosures) in the Background of the Invention,Detailed Description, and Examples is hereby incorporated herein byreference. Further, the hard copy of the sequence listing submittedherewith and the corresponding computer readable form are bothincorporated herein by reference in their entireties.

1 343 1 733 DNA Homo sapiens 1 gggatccgga gcccaaatct tctgacaaaactcacacatg cccaccgtgc ccagcacctg 60 aattcgaggg tgcaccgtca gtcttcctcttccccccaaa acccaaggac accctcatga 120 tctcccggac tcctgaggtc acatgcgtggtggtggacgt aagccacgaa gaccctgagg 180 tcaagttcaa ctggtacgtg gacggcgtggaggtgcataa tgccaagaca aagccgcggg 240 aggagcagta caacagcacg taccgtgtggtcagcgtcct caccgtcctg caccaggact 300 ggctgaatgg caaggagtac aagtgcaaggtctccaacaa agccctccca acccccatcg 360 agaaaaccat ctccaaagcc aaagggcagccccgagaacc acaggtgtac accctgcccc 420 catcccggga tgagctgacc aagaaccaggtcagcctgac ctgcctggtc aaaggcttct 480 atccaagcga catcgccgtg gagtgggagagcaatgggca gccggagaac aactacaaga 540 ccacgcctcc cgtgctggac tccgacggctccttcttcct ctacagcaag ctcaccgtgg 600 acaagagcag gtggcagcag gggaacgtcttctcatgctc cgtgatgcat gaggctctgc 660 acaaccacta cacgcagaag agcctctccctgtctccggg taaatgagtg cgacggccgc 720 gactctagag gat 733 2 5 PRT Homosapiens MISC_FEATURE (3) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 2 Trp Ser Xaa Trp Ser 1 5 3 86 DNAHomo sapiens 3 gcgcctcgag atttccccga aatctagatt tccccgaaat gatttccccgaaatgatttc 60 cccgaaatat ctgccatctc aattag 86 4 27 DNA Homo sapiens 4gcggcaagct ttttgcaaag cctaggc 27 5 271 DNA Homo sapiens 5 ctcgagatttccccgaaatc tagatttccc cgaaatgatt tccccgaaat gatttccccg 60 aaatatctgccatctcaatt agtcagcaac catagtcccg cccctaactc cgcccatccc 120 gcccctaactccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat 180 ttatgcagaggccgaggccg cctcggcctc tgagctattc cagaagtagt gaggaggctt 240 ttttggaggcctaggctttt gcaaaaagct t 271 6 32 DNA Homo sapiens 6 gcgctcgagggatgacagcg atagaacccc gg 32 7 31 DNA Homo sapiens 7 gcgaagcttcgcgactcccc ggatccgcct c 31 8 12 DNA Homo sapiens 8 ggggactttc cc 12 9 73DNA Homo sapiens 9 gcggcctcga ggggactttc ccggggactt tccggggactttccgggact ttccatcctg 60 ccatctcaat tag 73 10 256 DNA Homo sapiens 10ctcgagggga ctttcccggg gactttccgg ggactttccg ggactttcca tctgccatct 60caattagtca gcaaccatag tcccgcccct aactccgccc atcccgcccc taactccgcc 120cagttccgcc cattctccgc cccatggctg actaattttt tttatttatg cagaggccga 180ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg gaggcctagg 240cttttgcaaa aagctt 256 11 1679 DNA Homo sapiens misc_feature (1656) nequals a,t,g, or c 11 gcagcgcacc cgggcgatcg cttcacggat gcggacgacgtagccatcct tacctacgtg 60 aaggaaaatg cccgctcgcc cagctccgtc accggtaacgccttgtggaa agcgatggag 120 aagagctcgc tcacgcagca ctcgtggcag tccctgaaggaccgctacct caagcacctg 180 cggggccagg agcataagta cctgctgggg gacgcgccggtgagcccctc ctcccagaag 240 ctcaagcgga aggcggagga ggacccggag gccgcggatagcggggaacc acagaataag 300 agaactccag atttgcctga agaagagtat gtgaaggaagaaatccagga gaatgaagaa 360 gcagtcaaaa agatgcttgt ggaagccacc cgggagtttgaggaggttgt ggtggatgag 420 agccctcctg attttgaaat acatataact atgtgtgatgatgatccacc cacacctgag 480 gaagactcag aaacacagcc tgatgaggag gaagaagaagaagaagaaaa agtttctcaa 540 ccagaggtgg gagctgccat taagatcatt cggcagttaatggagaagtt taacttggat 600 ctatcaacag ttacacaggc cttcctaaaa aatagtggtgagctggaggc tacttccgcc 660 ttcttagcgt ctggtcagag agctgatgga tatcccatttggtcccgaca agatgacata 720 gatttgcaaa aagatgatga ggataccaga gaggcattggtcaaaaaatt tggtgctcag 780 aatgtagctc ggaggattga atttcgaaag aaataattggcaagataatg agaaaagaaa 840 aaagtcatgg taggtgaggt ggttaaaaaa aattgtgaccaatgaacttt agagagttct 900 tgcattggaa ctggcactta ttttctgacc atcgctgctgttgctctgtg agtcctagat 960 ttttgtagcc aagcagagtt gtagaggggg ataaaaagaaaagaaattgg atgtatttac 1020 agctgtcctt gaacaagtat caatgtgttt atgaaaggaagatctaaatc agacaggagt 1080 tggtctacat agtagtaatc cattgttgga atggaacccttgctatagta gtgacaaagt 1140 gaaaggaaat ttaggaggca taggccattt caggcagcataagtaatctc ctgtcctttg 1200 gcagaagctc ctttagattg ggatagattc caaataaagaatctagaaat aggagaagat 1260 ttaattatga ggccttgaac acggattatc cccaaacccttgtcatttcc cccagtgagc 1320 tctgatttct agactgcttt gaaaatgctg tattcattttgctaacttag tatttgggta 1380 ccctgctctt tggctgttct ttttttggag cccttctcagtcaagtctgc cggatgtctt 1440 tctttaccta cccctcagtt ttccttaaaa cgcgcacacaactctagaga gtgttaagaa 1500 taatgttact tggttaatgt gttatttatt gagtattgtttgtgctaagc attgtgttag 1560 atttaaaaaa ttagtggatt gactccactt tgttgtgttgttttcattgt tgaaaataaa 1620 tataactttg tattcgaaaa aaaaaaaaaa aaaatnrctgcggnccgaca agggaattc 1679 12 1963 DNA Homo sapiens misc_feature (335) nequals a,t,g, or c 12 ggatcctcgc ggcggcggcg gtgcttacag cctgagaagagcgtctcgcc cgggagcggc 60 ggcggccatc gagacccacc caaggcgcgt ccccctcggcctcccagcgc tcccaagccg 120 cagcggccgc gccccttcag ctagctcgct cgctcgctctgcttccctgc tgccggctgc 180 gcatggcktt ggcgttggcg gcgctggcgg cggtcgagccgcctgcgcag ccggtaccag 240 cagttgcaga atgaagaaga gtctggagaa cctgaacaggctgcaggtga tgctcctcca 300 ccttacagca gcatttctgc agagagcgca gcatnattttgactacaagg atgagtctgg 360 gtttccaaag cccccatctt acaatgtagc tacaacactgcccagttatg atgaagcgga 420 gaggaccaag gctgaagcta ctatcccttt ggttcctgggagagatgagg attttgtggg 480 tcgggatgat tttgatgatg ctgaccagct gaggataggaaatgatggga ttttcatgtt 540 aacttttttc atggcattcc tctttaactg gattgggtttttcctgtctt tttgcctgac 600 cacttcagct gcaggaaggt atggggccat ttcaggatttggtctctctc taattaaatg 660 gatcctgatt gtcaggtttt ccacctattt ccctggatattttgatggtc agtactggct 720 ctggtgggtg ttccttgttt taggctttct cctgtttctcagaggattta tcaattatgc 780 aaaagttcgg aagatgccag aaactttctc aaatctccccaggaccagag ttctctttat 840 ttattaaaga tgttttctgg caaaggcctt cctgcatttatgaattctct ctcaagaagc 900 aagagaacac ctgcaggaag tgaatcaaga tgcagaacacagaggaataa tcacctgctt 960 taaaaaaata aagtactgtt gaaaagatca tttctctctatttgttccta ggtgtaaaat 1020 tttaatagtt aatgcagaat tctgtaatca ttgaatcattagtggttaat gtttgaaaaa 1080 gctcttgcaa tcaagtctgt gatgtattaa taatgccttatatattgttt gtagtcattt 1140 taagtagcat gagccatgtc cctgtagtcg gtagggggcagtcttgcttt attcatcctc 1200 catctcaaaa tgaacttgga attaaatatt gtaagatatgtataatgctg gccattttaa 1260 aggggttttc tcaaaagtta aacttttgtt atgactgtgtttttgcacat aatccatatt 1320 tgctgttcaa gttaatctag aaatttattc aattctgtatgaacacctgg aagcaaaatc 1380 atagtgcaaa aatacattta aggtgtggtc aaaaataagtctttaattgg taaataataa 1440 gcattaattt tttatagcct gtattcacaa ttctgcggtaccttattgta cctaagggat 1500 tctaaaggtg ttgtcactgt ataaaacaga aagcactaggatacaaatga agcttaatta 1560 ctaaaatgta attcttgaca ctctttctat aattagcgttcttcaccccc acccccaccc 1620 ccacccccct tattttcctt ttgtctcctg gtgattaggccaaagtctgg gagtaaggag 1680 aggattaggt acttaggagc aaagaaagaa gtagcttggaacttttgaga tgatccctaa 1740 catactgtac tacttgcttt tacaatgtgt tagcagaaaccagtgggtta taatgtagaa 1800 tgatgtgctt tctgcccaag tggtaattca tcttggtttgctatgttaaa actgtaaata 1860 caacagaaca ttaataaata tctcttgtgt agcacctttaaaaaaaaaaa aaaaaaaaaa 1920 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaanaaaa 1963 13 1212 DNA Homo sapiens 13 tgtttgaagt tgttactttt gtttacagcaaagtttgatg tagtgtgcag tagtgagctc 60 tagactgatc tttttctaaa tcagaaagtgattaaagtat gcacaaccaa aggcaggttt 120 ttctttttca tttattcagc aactatttattaagcatcaa ctctgtgcca ggcacgttac 180 tagctgctac atactgtctg aacatgacatacggttaagt aactttacaa ttattatcaa 240 atacttcaat gtagatattt cttaagttgaaatagcatta actaggataa tgctttcatg 300 ttattttatt tgtcttgtga tagaaattcaactttgtacc atcttaaaac taggttgcta 360 taaaaatagg aggatgaagt caataaagtttatgccagtt taaaaactgg aaggaaaagg 420 taagagctct ccattataaa atagttgcattcggttaatt tttacacatt agtgcattgc 480 gtatatcaac tggccctcaa tgaagcatttaagtgcttgg aattttacta aactgacttt 540 tttgcaactt tgggagattt ttgaggggagtgttgaaaat tgccaaacac tcacctctta 600 ctcaaaactt caaataaaat acacattttcaagagggagc accttttata tttgataagt 660 tttcattata aaccttataa taccagtcacaaagaggttg tctgtctatg gtttagcaaa 720 catttgcttt tctttttgga agtgtgattgcaattgcaga acagaaagtg agaaaacact 780 gccagcggtg attgctactt gaggtagttttttacaacta ccatttcccc tccatgaaat 840 tatgtgaaat ttattttatc tttgggaaaagttgagaaga tagtaaaaga attaggaatt 900 taaaattaca gggaaaaata tgtaagtgaaaagcaataaa tattttgttc actttgctat 960 caagatgttc actatcagat atttattatatggcagcaat ttatattttt aatcattgcc 1020 cattaataga cgcagtaaaa tatttttgaatcagacattt ggggtttgta tgtgcattaa 1080 aattgtcttt tgtactgtaa gttactgttaatttgaatat tttattgaac tgtctccctg 1140 tgcctttata atataaagtt gtttctacaacttttaatga tcttaataaa gaatacttta 1200 agaaaaaaaa aa 1212 14 2061 DNAHomo sapiens misc_feature (1703) n equals a,t,g, or c 14 ggttttcctccgacttccgg acatctccct gggagtcgcg cagagtggag tcaaaggcaa 60 ccagtgctcgctgcggtctc tggggatcgg gaccgcggcg gcggcccgcg agcgggatgt 120 tccggggcttgagcagttgg ttgggcttgc agcagccggt ggcaggcggt gggcagccca 180 atggagatgctccacccgag cagccgtccg agacggtggc tgagtctgcg gaggaggagc 240 tgcagcaagcgggagaccag gagctcctcc accaggccaa agacttcggc aactatttat 300 ttaactttgcatctgctgcc acaaaaaaga taactgaatc agttgctgaa acagcacaaa 360 caataaagaaatccgtagaa gaaggaaaaa tagatggcat cattgacaag acaattatag 420 gagattttcagaaggaacag aaaaaatttg ttgaagagca acatacaaag aagtcagaag 480 cagctgtgcccccatgggtt gacactaacg atgaagaaac aattcaacaa caaattttgg 540 ccttatcagctgacaagagg aatttccttc gtgaccctcc ggctggcgtg caatttaatt 600 tcgactttgatcagatgtac cccgtggccc tggtcatgct ccaggaggat gagctgctar 660 caagatgagatttgccctcg ttcctaaact tgtgaaggaa gaagtgttct ggaggaacta 720 cttttaccgcgtctccctga ttaagcagtc agcccagctc acggccctgg ctgcccaaca 780 gcaggccgcagggaagggag gagaagagca atggcagaga gcaagatttg ccgctggaga 840 ggcagtacggcccaaaacgc cacccgttgt aatcaaatct cagcttaaaa ctcaagagga 900 tgaggaagaaatttctacta gcccaggtgt ttctgagttt gtcagtgatg ccttcgatgc 960 ctgtaacctaaatcaggaag atctaaggaa agaaatggag caactagtgc ttgacaaaaa 1020 gcaagaggagacagccgtac tggaagagga ttctgcagat tgggaaaaag aactgcagca 1080 ggaacttcaagaatatgaag tggtgacaga atctgaaaaa cgagatgaaa actgggataa 1140 ggaaatagagaaaatgcttc aagaggaaaa ttagctgttc ctgaaataga agaataatcc 1200 ttaacagtctgcaaactgac attaaattct agatgttgac aattactgaa tcagaaggca 1260 tgaaagagtataattttatg aaattcaaaa ttattctttt ttcaagttga aacttgcctc 1320 ttctactttaaaaaagtata tagaacagtt acttctaata atcagaaaga gatgttttat 1380 agaacatttctttaatataa agttagagat gtcttcatag gcagtatggc tatctttgcc 1440 acagaaacataagtaaaatt ttagagttct gttttccatg aggtcaaaaa tataatttat 1500 tcctcagtcatggttttcta aatatctgta ctccacattc cattttaatt gatatgaggg 1560 tgttaaagtacctacttaat gggttgatta ctatcaaaat gaccaaatta taccaaagaa 1620 cttaagaggaagcactttca gaactattca cttgccaggt attttctaaa attccacctg 1680 aaagccaaaagataaaatac atnagttgga ttttaatgat ataagcatca cacaatttta 1740 cattaagaaatactgtgcag cccatgcgtg gtggctcagg cctgtaatcc cagcantttg 1800 ggaggccgaggtgggcagat caccggaggt caggagttcg agaccagcct tgccaacata 1860 gtgaaaccctgtctttacta aaaatacaaa aattagccgg gcatggtggc aggcacctgt 1920 aatcccagctactagggagg cttttgaacc caggaggcag aggttgcagc gagctgagat 1980 cgcgccactgcactccagcc tgggtgatag agtgagattc agtctcaaaa aaaaaaaaaa 2040 aaaaaaaaaaaatgacctcg a 2061 15 1412 DNA Homo sapiens misc_feature (1362) n equalsa,t,g, or c 15 cccttcatct gcgttgccag gaaccctgtc agcagaaact tctcaagccccatccttgcc 60 aggaagctct gtgaaggtgc tgctgatgac ccagattcct ccatggtcctcctgtgtctc 120 ctgttggtgc ccctcctgct cagtctcttt gtactggggc tatttctttggtttctgaag 180 agagagagac aagaagagta cattgaagag aagaagagag tggacatttgtcgggaaact 240 cctaacatat gcccccattc tggagagaac acagagtacg acacaatccctcacactaat 300 agaacaatcc taaaggaaga tccagcaaat acggtttact ccactgtggaaataccgaaa 360 aagatggaaa atccccactc actgctcacg atgccagaca caccaaggctatttgcctat 420 gagaatgtta tctagacagc agtgcactcc cctaagtctc tgctcaaaaaaaaaacaatt 480 ctcggcccaa agaaaacaat cagaagaatt cactgatttg actagaaacatcaaggaaga 540 atgaagaacg ttgacttttt tccaggataa attatctctg atgcttctttagatttaaga 600 gttcataatt ccatccactg ctgagaaatc tcctcaaacc cagaaggtttaatcacttca 660 tcccaaaaat gggattgtga atgtcagcaa accataaaaa aagtgcttagaagtattcct 720 ataaaaatgt aaatgcaagg tcacacatat taatgacagc ctgttgtattaatgatggct 780 ccaggtcagt gtctggagtt tcattccatc ccagggcttg gatgtcaggattataccaag 840 agtcttgcta ccaggagggc aagaagacca aaacagacag acaagtccagcagaagcaga 900 tgcacctgac aaaaatggat gtattaattg gctctataaa ctatgtgcccagcaytatgc 960 tgagcttaca ctaattggtc agacatgctg tctgccctca tgaaattggctccaaatgaw 1020 tgaactactt tcatgagcag ttgtagcagg cctgaccaca gattcccagagggccaggtg 1080 tggatccaca ggacttgaag gtcaaagttc acaaagatga agaatcagggtagctgacca 1140 tgtttggcag atactataat ggagacacag aagtgtgcat ggcccaaggacaaggacctc 1200 cagccaggct tcatttatgc acttgtctgc aaaagaaaag tctaggttttaaggctgtgc 1260 cagaacccat cccaataaag agaccgagtc tgaagtcaca ttgtaaatctagtgtaggag 1320 acttggagtc aggcagtgag actggtgggg cacggggggc antgggtantgtaaaccttt 1380 taaagatggt taattcntca ttagtgtttt tt 1412 16 1052 DNAHomo sapiens 16 ttcctctcct ctctctaccc ctcctgtctc tcctcccctc ctctctcttcctctcctctc 60 tctcttcctc tcctctctct tcccttcctg tctctcttcc cctcctctctctcttcctgt 120 cctctatctc ttcccctcct ctatctcttc ctctcctctc tctcttcctctcctctctct 180 ctcttscttt cttctctctc tcctgtctcg gctgttgtgg gttgcaggttgggtgctgct 240 gttgtggtcc ttcccagaaa ctgccagtag agggcagcct gggcatcctaatgcttactc 300 tggttgttac acaaagaaaa tattggggtc actggcgagc ccacccacactcaccagaat 360 ctccactgta gtccccctaa caaacagccc ttcacttcct ctcccacttcagcaatttgt 420 attttgatgc cattggcctc agatcagagt gttttaaatc atcacgccctggcttatccc 480 tggtcgagcc aggacacggg gtgcttcagt gggtctgtca ccctctctccttgaagcatg 540 ttgcttttat ttatttactt ttactctcac cctgctcctg taccagcaggggccacttca 600 aagccaaggt acagggtgat aacttgtggt ccagcatcag ttttctccacttctttctcc 660 cactcacccc cagcaaggtg cctggggaga cttgagcaga tgtttcattttggcctggcc 720 agtggctgaa agcaggcctc caatgcactg tgacctctgg cttccccagcagctttccca 780 gagaggcaga ggggccttcc acagcccggg ttctcctgct gcctcctgcctgctgcagct 840 gcaggcattc tgaggggcaa cgtggaggaa gggccaggga tgcatgggattttaattgtt 900 tcatcacacc ttccccgtgg caaagaaaca gtcagtcctc ttcaggtgtcttctggattt 960 ctggtgatgg acagagaaat ctttttacag tttcaaatta tgttcaacaaataaaaattg 1020 cattttttat tttggaaaaa aaaaaaaaaa aa 1052 17 683 DNA Homosapiens 17 aattcggcag aggcacttat catgtacata tagcctgttt tttagcattgttagacaaag 60 taggcatatt cctttccatc caagaactca taacctagta attgtagttggctgatagct 120 cattgcccat acacaaggat ctaacacaac ctcttgaata aacatcccccttattcagaa 180 atgccttttc ctatttccat attgcaactt tgcttacaaa tttccaatctgtctttctgt 240 ttacagaaga tatacaaaat tccttttgta tgatctcttt atatctcttgattttctttt 300 gtgtttgcta ccaaagggcc tgcacatagt gagaagattg tgcatgatctgtgagctcta 360 ccacacctgg aattagggat caccaatatg agaaaaaaaa ttggaggtacaaataacatt 420 atcatatgtw attggcatat aaattacaga tgtwtctatg actaaaaaccctgtggatat 480 waaccmaatg cagataawtw taataaaatw twtaaaaatw twatcmaataatgatagtgc 540 tattcaaata cttcaaattt gcacagtgat ttatttctta aaatatgttaacacatgtga 600 gccaatacac tgaggtcact ggataaataa acagattctt gcaaaaaaaaaaaaaaaaaa 660 actcgagggg ggcccgtacc ctt 683 18 1054 DNA Homo sapiensmisc_feature (74) n equals a,t,g, or c 18 aaactcattt aggtgacactatagaaggta cgcctgcagg taccggtccg gaattcccgg 60 gtcgacccac gmgnccggcgacaagatggc agcagcgtgt cggagcgtga agggcctggt 120 ggcggtaata accggaggagcctcgggcct gggcctggcc acggcggacg acttgtgggg 180 cagggagcct ctgctgtgcttctggacctg cccaactcgg gtggggaggc ccaagccaag 240 aagttaggaa acaactgcgttttcgcccca gccgacgtga cctctgagaa ggatgtgcaa 300 acagctctgg ctctagcaaaaggaaagttt ggccgtgtgg atgtagctgt caactgtgca 360 ggcatcgcgg tggctagcaagacgtacaac ttaaagaagg gccagaccca taccttggaa 420 gacttccagc gagttcttgatgtgaatctc atgggcacct tcaatgtgat ccgcctggtg 480 gctggtgaga tgggccagaatgaaccagac cagggaggcc aacgtggggt catcatcaac 540 actgccagtg tggctgccttcgagggtcag gttggacaag ctgcatactc tgcttccaag 600 gggggaatag tgggcatgacactgcccatt gctcgggatc tggctcccat aggtatccgg 660 gtgatgacca ttgccccaggtctgtttggc accccactgc tgaccagcct cccagagaaa 720 gtgtgcaact tcttggccagccaagtgccc ttccctagcc gactgggtga ccctgctgag 780 tatgctcacc tcgtacaggccatcatcgag aacccattcc tcaatggaga ggtcatccgg 840 ctggatgggg ccattcgtatgcagccttga agggagaagg cagagaaaac acacgctcct 900 ctgcccttcc tttccctggggtactactct ccagcttggg aggaagccca gtagccattt 960 tgtaactgcc taccagtcgccctctgtgcc taataaagtc tctttttctc acanaaaaaa 1020 aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa aaaa 1054 19 1393 DNA Homo sapiens misc_feature (127) nequals a,t,g, or c 19 ggaacaagct gggatatgtg agcgttaagc tactcacatccttcaaaaag gtgaaacatc 60 ttacacggga ctggagaacc acagcacatg ctttgaagtattcagtggtc cttgagttga 120 atgaggncca ccggaaggtg aggaggacca cccccgtcccactgttcccc aacgagaacc 180 tccccagcaa gatgctcctg gtctatgatc tctacttgtytcctaagctg tgggctctgg 240 ccacccccca gaagaatggg aagggtgcaa garaaggtgatggaacacct gctcaagctt 300 tttgggactt ttggagtcat ctcatcagtg cggatcctcaaacctgggag agagctgccc 360 cctgacatcc ggaggntcca gcagccgcta cagctcctctgaccccgaga gcaaccccac 420 atcccctatg gcgggccgac ggcacgngkc caccaacaagctcagcccgt ctggccacca 480 gaatctcttt ctgagtccaa atgcctcccc gtgcacaagtccttggagca gccccttggc 540 ccaacgcaaa ggcgtttcca gaaagtcccc actggcggaggaaggtagac tgaactgcag 600 caccagccct gagatcttcc gcaagtgtat ggattattcctctgacagca gcgtcactcc 660 ctctggcagc ccctgggtcc ggaggcgtcg ccaagccgagatggggaccc aggagaaaag 720 ccccggtacg agtcccctgc tctcccggaa gatgcagactgcagatgggs tacccgtagg 780 tngcttgagg ttgcccaggg gtcctgacaa caccagaggatttcatggcc atgagaggag 840 cagggcctgt gtataaatac cttctatttt taatacaagctccactgaaa accaccttcg 900 ttttcaaggt tctgacaaac acctggcatg acagaatggaattcgttccc ctttgagaga 960 ttttttattc atgtagacct cttaatttat ctatctgtaatatacataaa tcggtacgcc 1020 atggtttgaa gaccaccttc tagttcagga ctcctgttcttcccagcatg gccactattt 1080 tgatgatggc tgatgtgtgt gagtgtgatg gccctgaagggctgtaggac ggaggttccc 1140 tgggggaagt ctgttctttg gtatggaatt tttctctcttctttggtatg gaatttttcc 1200 cttcagtgac tgagctgtcc tcgataggcc atgcaagggcttcctgagag ttcaggaaag 1260 ttctcttgtg caacagcaag tagctaagcc tatagcatggtgtcttgtag gaccaaatcg 1320 atgttacctg tcaagtaaat aaataataaa acacccaactgggagtgctg aaaaaaaana 1380 annaaaaaac tcg 1393 20 1215 DNA Homo sapiensmisc_feature (15) n equals a,t,g, or c 20 aggaaaagtt ttccnaattggaaagcgggc agtgagcgca acgcaattaa tgtgagttag 60 ntcantcatt aggcaccccaggctttacac tttatgcttc cggntcgtat gttgtgtgga 120 attgtgagcg gataacaatttcacacagga aacagctatg accatgatta cgccaagctn 180 taatacgact cactatagggaaagctggta cgcctgcagg taccggtccg gaattcccgg 240 gtcgacccac gcgtccgcccacgcgtccgt gaaaatccga agtgccgcgg aaagtggagg 300 tgagggccgc ccgccctagaggtgcccgtc cgagaggcag agctgacaag gaaggtttcg 360 agcgttttgc tggcaaagggatttcttaca acctccaggc atgcgtcttt ctgccctgct 420 ggccttggca tccaaggtcactctgccccc ccattaccgc tatgggatga gccccccagg 480 ctctgttgca gacaagaggaagaacccccc atggatcagg cggcgcccag tggttgtgga 540 acccatctct gatgaagactggtatctgtt ctgtggggac acggtggaga tcctagaagg 600 caaggatgcc gggaagcagggcaaagtggt tcaagttatc cggcagcgaa actgggtggt 660 cgtgggaggg ctgaacacacattaccgcta cattggcaag accatggatt accggggaac 720 catgatccct agtgaagcccccttgctcca ccgccaggtc aaacttgtgg atcctatgga 780 caggaaaccc actgagatcgagtggagatt tactgaagca ggagagcggg tacgagtctc 840 cacacgatca gggagaattatccctaaacc cgaatttccc agagctgatg gcatcgtccc 900 tgaaacgtgg attgatggccccaaagacac atcagtggaa gatgctttag aaagaaccta 960 tgtgccctgt ctaaagacactgcaggagga ggtgatggag gccatgggga tcaaggagac 1020 ccggaaatac aagaaggtctattggtattg agcctggggc agagcagctc ctccccaact 1080 tctgtcccag ccttgaaggctgaggcactt ctttttcaga tgccaataaa gagcacttta 1140 tgagtcctcc aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1200 aaaaggggcg gccgc 121521 2042 DNA Homo sapiens 21 ctgcatccag gcgcagaata acctgggtat cttgtggtctgaaagagaga aattgaaact 60 gcacaggctt acctagagtc atcagaagca ctatataatcagtatatgaa agaggttggg 120 agtcctcctc ttgatcctac tgagcgtttt cttctgaagaagagaaactt actgaacaag 180 agagatcaaa aagatttgaa aaggtttata ctcataacctatattaccta gctcaagtct 240 accagcatct ggaaatgttt gagaaggctg ctcactattgccatagtaca ctaaaacgcc 300 agcttgagca caatgcctac catcctatag agtgggctatcaatgctgct accttgtcac 360 agttttacat caataagcta tgctttatgg aggccaggcactgtttatca gctgctaatg 420 tcatttttgg tcaaactgga aagatctcag ccacagaagacactcctgaa gctgaaggag 480 aagtgccaga gctttatcat caaagaaagg gggaaatagcaaggtgctgg atcaaatact 540 gtttgactct catgcagaat gcccaactct ccatgcaggacaacatagga gagcttgatc 600 ttgataaaca gtctgaactt agagctttaa ggaaaaaagaactagatgag gaggaaagca 660 ttcggaaaaa agctgtgcag tttggaaccg gtgaactgtgtgatgccatc tctgcagtag 720 aagagaaagt gagctacttg agacctttag attttgaagaagccagagaa cttttcttat 780 tgggtcagca ctatgtcttt gaggcaaaag agttctttcagattgatggt tatgtcactg 840 accatattga agttgtccaa gaccacagtg ctctgtttaaggtgcttgca ttctttgaaa 900 ctgacatgga gagacggtgc aagatgcata aacgcrgaatagccatgcta gagcccctaa 960 ctgtagacct gaatccacag tattatctgt tggtcaacagacagatccag tttgaaattg 1020 cacatgctta ctatgatatg atggatttga aggttgccattgctgacagg ctaagggatc 1080 ctgattcaca cattgtaaaa aaaataaata atcttaataagtcagcactg aagtactacc 1140 agctcttctt agactccctg agagacccaa ataaagtattccctgagcat ataggggaag 1200 atgttcttcg ccctgccatg ttagctaagt ttcgagttgcccgtctctat ggcaaaatca 1260 ttactgcaga tcccaagaaa gagctggaaa atttggcaacatcattggga acattacaaa 1320 tttattgttg attactgtga aaagcatcct gaggccgcccaggaaataga agttgagcta 1380 gaacttagta aagagatggt tagtcttctc ccaacaaaaatggagagatt cagaaccaag 1440 atggccctga cttaatcctt gtttttaaag aaaggaaatgtgcaatattg aagtgatctt 1500 tttccctagt cagacaggcc caattccatt gtgatgtttacctttatagc caggtgagtg 1560 cagtttgaac ttgagataca gtcaactgag tgtttgctaggatcctaagg aacataaagt 1620 taattaaaaa cttacaccta attatgtaaa ttgccttgttaaagacatgt gatttgtatt 1680 ttagatgctt gtttcctatt aaaatacaga catttctaccctcagtttct aaatgtagac 1740 tatttgttgg ctagtacttg atagattcct tgtaagaaaaaatgctgggt aatgtacctg 1800 gtaacaagcc tgttaatata ttaagattga aaaagtaacttctatagtta ctccttctaa 1860 aatatttgac ttcctacatt ccccccaccc aaaatctttcccttttgaaa atactaaaaa 1920 ctaagttatg ttattataaa gtgtaaaatg gtttgtcttaattataggag aaaaaggcct 1980 tgttagaaat aaaataaact gacttatttc actaatgaaaaaaaaaaaaa aaaaaaaaaa 2040 tt 2042 22 1872 DNA Homo sapiens misc_feature(1871) n equals a,t,g, or c 22 gggtcgaccc acgcgtccga ttggcctagagctcctgtga ccgagagcgc cacggaagcc 60 tggggatgat gtcgggcagc tttattctttgcttggcttt ggtaactagg tggtcccctc 120 aagcatcctc agttcctctt gctgtttatgaatctaagac aaggaagtcc tatagaagcc 180 aaagggacag ggacggaaag gacaggtcccaagggatggg gctgtcttta cttgtggaaa 240 ccaggaaatt gctcctctca gccaaccaaggttgaccaca caccaccctt ccggagcagc 300 tcagtcagcc ctcggggacg rgaaaccacaagcgcagaga cgctgaggcc caggcaggtg 360 aagaggaagt ggctttgggt ttttaaagtaggtgagcgtg acctctctga ctgcttcttc 420 cccggggggg actgcaaacc gctcagggttgcggcagagc catggacttc cggtccctgc 480 aacgggtgac ctaagcgtgg tgcacccatcagtcacgcag gaggactgac ttgacagacg 540 aaagacaagc ccggatgaca cagggtgagaagagtcaggg ccgcacctct gtccctgcaa 600 accaacaggt gcatggtgag tgtggcagtccccacagctc cacaatgggc tcccccgcca 660 acggggacga cagggatctt caggaacttctgacctcacc aagtcaagtg gaccactctc 720 cactccacga ggatgtgaaa cggttctttaaaatgggatt ttagagcctc gggaatgcat 780 gtgcgtcgca tctttcatat tatgggtcaggatagattca tttcttgcaa catagtggaa 840 aagatataag ctgcagtaat ttgctctttgaatgaccgtc acccccagta taggatatgc 900 ttgtatcccc ccgtcactcc tccgcctgttttttaaactt ttccaccacc tgcgtccaaa 960 aagaatgtta tagcgagtgc tcttaaatgttgaacctggg tgttgcttcc gggccagtct 1020 gcgtggctcc atgaaaagct cactgctgccccagccgggc ttcttagagg aggtcagttg 1080 tcctatgtat catcatttac tctgggaatcctactgtgaa atcatgtctg tatttttctg 1140 gagcagttca catagagtag aatgtggaatttcccgtgaa cgtctccttc ctcccccgta 1200 tctgccgcct gtcacttcgc caccgtgctagaatactgtt gtgttgtaag atgactaatt 1260 ttaaaagaac ctgccctgaa aagttcttagaaacgcaatg aaagggagga acttgtcctt 1320 tacccagttt ttcctttgta ggatgggaaagtataaaaag gcacagaagg ttgtcatggg 1380 ctgttccttg ggggttttta tcctgctcaccgtggagata agcctgcggc ttgtctaacc 1440 agcgcagcgm aaaggtctca atgccttttggtaacatccg tcattgcaga agaaagttta 1500 cacgacgtca aaaagtgacg ttcatgctaagtgtttttcc agaaatattg gtttcatgtt 1560 tcttattkgc tctgcctcct gtgcttatatcatccaaaaa ctttttaaaa aggtccagaa 1620 ttctatttta acctgatgtt gagcacctttaaaacgttcg tatgtgtgtt gcactaattc 1680 taaactttgg aggcattttg ctgtgtgaggccgatcgcca ctgtaaaggt cctagagttg 1740 cctgtttgtc tctggagatg gaattaaaccaaataaagag cttccactgg aggcttgtat 1800 tgaccttgta actatatgtt aatctcgtgttaaaataaaa tataacttgt gaaaaaaaaa 1860 aaaaaaaaac nt 1872 23 289 DNA Homosapiens misc_feature (284) n equals a,t,g, or c 23 catttaccca cctatcaacatgtttgcttt ctcttttgtt ggtgagaatg agtggcttct 60 tgctcctagc tagagccagtccttccatat gtgctttaga ttcttcctgt tttgttcaag 120 aatattgctc aagctattcttcctcctgtt tcctgcatca gcatttcccc tctctactag 180 atcatctctg tcagtaaatgaacatgttgt tgtttctcct agaagtactg tttctatatc 240 tagatagtac tctagctagagttaaaaaaa aaaaaaaaaa cctnggggg 289 24 3533 DNA Homo sapiensmisc_feature (44) n equals a,t,g, or c 24 ttttatttac ttcaaattaactgtacttta ctcaaataga aaangaataa ttttcacatt 60 atgaagctac acaattccaaaatacacatg ctgaggctct ttttaagtcc gaattgtcta 120 gtaattacaa aaaagtgaagagtttacaga tatacaagga aataaaggcg aattattgca 180 aagaaaacaa gtttaatttcactttgaatg acaacgattt ttctggaaag cagatacttc 240 actcctttaa gtttccacccaagccacaat aatttcaaac ggtcttgcgg atgacccagc 300 tggtcactct tgtttatgtggggactggag gtaatgagag ccaaaaaaag tgctataaac 360 ctaatttggc tagagcaagttcacacgaca cgaccgtgct ttaaaaactt gctctccatt 420 atgtacttcc ttccatcaggttggggaaaa aaaaatggtg gggatggtga gtaaacacac 480 cagtggtttc atcagaggggaactcactac tcaggaggtg acggtgacgt ggtgccggtc 540 cctgaagtac gcgcacaagctccggaggtt gcgggagctt ccgctgccgc ctggagggaa 600 gccggagcga cgggggtcacggcggcggtc agagggtaaa ggtcttgctc ccagcagcct 660 ccgcggtgga tacgtcgccatcttggatcc gcgggacaag aaaattcatg cgagggagac 720 gtggtgggcg gtccttcctgtgacacgacc cttgagtgac agttctattt gattgcctcc 780 ggtactgtga ggaaaggacacgactctatg gtgaggactg atggacatac attatctgag 840 aaaagaaact accaggtgacaaacagcatg tttggtgctt caagaaagaa gtttgtagag 900 ggggtcgaca gtgactaccatgacgaaaac atgtactaca gccagtcttc tatgtttcca 960 catcggtcag aaaaagatatgctggcatca ccatctacat caggtcagct gtctcagttt 1020 ggggcaagtt tatacgggcaacaaagtgca ctaggccttc caatgagggg gatgagcaac 1080 aatacccctc agttaaatcgcagcttatca caaggcactc agttaccgag ccacgtcacg 1140 ccaacaacag gggtaccaacaatgtcactt cacacgcctc catctccaag caggggtatt 1200 ttgcctatga atcctargaatatgatgaac cactcccagg ttggtcaggg cattggaatt 1260 cctagcagga caaatagcatgagcagttca gggttaggta gccccaacag aagctcgcca 1320 agcataatat gtatgccaaagcagcagcct tctcgacagc cttttactgt gaacagtatg 1380 tctggatttg gaatgaacaggaatcaggca tttggaatga ataactcctt atcaagtaac 1440 atttttaatg gaacagacggaagtgaaaat gtgacaggat tggacctttc agatttccca 1500 gcattagcag accgaaacaggagggaagga agtggtaacc caactccatt aataaacccc 1560 ttggctggaa gagctccttatgttggaatg gtaacaaaac cagcaaatga acaatcccag 1620 gacttctcaa tacacaatgaagattttcca gcattaccag gctccagcta taaagatcca 1680 acatcaagta atgatgacagtaaatctaat ttgaatacat ctggcaagac aacttcaagt 1740 acagatggac ccaaattccctggagataaa agttcaacaa cacaaaataa taaccagcag 1800 aaaaaaggga tccaggtgttacctgatggt cgggttacta acattcctca agggatggtg 1860 acggaccaat ttggaatgattggcctgtta acatttatca gggcagcaga gacagaccca 1920 ggaatggtac atcttgcattaggaagtgac ttaacaacat taggcctcaa tctgaactct 1980 cctgaaaatc tctaccccaaatttgcgtca ccctgggcat cttcaccttg tcgacctcaa 2040 gacatagact tccatgttccatctgagtac ttaacgaaca ttcacattag ggataagctg 2100 gctgcaataa aacttggccgatatggtgaa gaccttctct tctatctcta ttacatgaat 2160 ggaggagacg tattacaacttttagctgca gtggagcttt ttaaccgtga ttggagatac 2220 cacaaagaag aacgagtatggattaccagg gcaccaggca tggagccaac aatgaaaacc 2280 aatacctatg agaggggaacatattacttc tttgactgtc ttaactggag gaaagtagct 2340 aaggagttcc atctggaatatgacaaatta gaagaacggc ctcacctgcc atccaccttc 2400 aactacaacc ctgctcagcaagccttctaa aaaaaaaaaa aaaaaaaaaa aaaaagactt 2460 cccttttctt ggggtatggctgtctcagca caatactcaa cataactgca gaactgatgt 2520 ggctcaggca ccctggttttaattccttga ggatctggca attggcttac gcaaaaggtc 2580 accatttgag gtcctgccttactaattatg tgctgcccaa caactaaatt tgtaatttgt 2640 ttttctctag tttgagcagggtctgaattt tttcatttat ttcctttttt gccagcagac 2700 agacttgagt ctgtaaagacaagcaaatac actgacagaa gtttaccata gtttctaaaa 2760 tgtaaaaaag aaaacccccaaaagactcaa gaaaattaga ccacaaattt tgcattgttc 2820 attgtagcac tattggtaataaaataacaa atgtttgtgc atttttatgt gaagatcctt 2880 ctcgtatttc atttggaaagatgagcaaga ggtctgcttc cttcatttta cttccccttc 2940 tgtttttgaa aggcagtttcgccaagctta atgcaagaat atctgactgt ttagaagaaa 3000 gatattgcca caatctctggatggttttcc agggttgtgt tattactgag cttcatcttt 3060 ccagaatgag caaaacactgtccagtcttt gttacgattt tgtaataaat gtgtacattt 3120 tttttaaatt tttggacatcacatgaataa aggtatgtat gtacgaatgt gtatatatta 3180 tatatatgac atctattttggaaaatgttt gccctgctgt acctcatttt taggaggtgt 3240 gcatggatgc aatatatgaaaatgggacat tctggaactg ctggtcaggg gactttgtcg 3300 ccctgtgcac taaaagggccagattttcag cagccaagga catccatacc caagtgaatg 3360 tgatgggact taaaagaagtgaactgagac aattcactct ggctgtttga acagcagcgt 3420 ttcataggaa gagaaaaaaagatcaatctt gtattttctg accacataaa ggcttcttct 3480 ctttgtaata aagtagaaaagctctcctca aaaaaaaaaa aaaaaaactc gag 3533 25 1148 DNA Homo sapiens 25acccacgcgt ccgcaaatta tacttcctca ttcatattat gttgatacaa aagaccttgg 60cagccatttc tcccagcagt tttaaaggat gaacattgga tttcatgcca tcccatagaa 120aacctgtttt aaaattttag ggatctttac ttggtcatac atgaaaagta cactgcttag 180aaattataga ctattatgat ctgtccacag tgcccattgt cacttctttg tctcatttct 240tccctttgtt ccttagtcat ccaaataagc ctgaaaacca taagagatat tactttattg 300aatatggttg gcattaaatt tagcatttca ttatctaaca aaattaatat aaattccagg 360acatggtaaa atgtgtttta ataaccccca gacccaaatg aaaatttcaa agtcaatacc 420agcagattca tgaaagtaaa tttagtccta taattttcag cttaattata aacaaaggaa 480caaataagtg gaagggcagc tattaccatt cgcttagtca aaacattcgg ttactgccct 540ttaatacact cctatcatca gcacttccac catgtattac aagtcttgac ccatccctgt 600cgtaactcca gtaaaagtta ctgttactag aaaattttta tcaattaact gacaaatagt 660ttctttttaa agtagtttct tccatcttta ttctgactag cttccaaaat gtgttccctt 720tttgaatcga ggtttttttg ttttgttttg ttttctgaaa aaatcataca actttgtgct 780tctattgctt ttttgtgttt tgttaagcat gtcccttggc ccaaatggaa gaggaaatgt 840ttaattaatg ctttttagtt taaataaatt gaatcattta taataatcag tgttaacaat 900ttagtgaccc ttggtaggtt aaaggttgca ttatttatac ttgagatttt tttcccctaa 960ctattctgtt ttttgtactt taaaactatg ggggaaatat cactggtctg tcaagaaaca 1020gcagtaatta ttactgagtt aaattgaaaa gtccagtgga ccaggcattt cttatataaa 1080taaaattggt ggtactaatg tgaaaaaaaa aaaaaaaaaa aactcgaggg gggcccggta 1140ccctatta 1148 26 717 DNA Homo sapiens 26 ggcacgagct agctgccgccacccgaacag cctgtcctgg tgccccggct ccctgccccg 60 cgcccagtca tgaccctgcgcccctcactc ctcccgctcc atctgctgct gctgctgctg 120 ctcagtgcgg cggtgtgccgggctgaggct gggctcgaaa ccgaaagtcc cgtccggacc 180 ctccaagtgg agaccctggtggagccccca gaaccatgtg ccgagcccgc tgcttttgga 240 gacacgcttc acatacactacacgggaagc ttggtagatg gacgtattat tgacacctcc 300 ctgaccagag accctctggttatagaactt ggccaaaagc aggtgattcc aggtctggag 360 cagagtcttc tcgacatgtgtgtgggagag aagcgaaggg caatcattcc ttctcacttg 420 gcctatggaa aacggggatttccaccatct gtcccagcgg atgcagtggt gcagtatgac 480 gtggagctga ttgcactaatccgagccaac tactggctaa agctggtgaa gggcattttg 540 cctctggtag ggatggccatggtgccagcc ctcctgggcc tcattgggta tcacctatac 600 agaaaggcca atagacccaaagtctccaaa aagaagctca aggaagagaa acgaaacaag 660 agcaaaaaga aataataaataataaatttt aaaaaaaaaa aaaaaaaaaa aaaaaaa 717 27 1099 DNA Homo sapiensmisc_feature (1030) n equals a,t,g, or c 27 ggcacgagcc gatgtggacatcatcctgtc tatccccatg ttcctgcgcc tgtacctgat 60 cgcccgagtc atgctgctgcacagcaagct cttcaccgat gcctcgtccc gcagcatcgg 120 ggccctcaac aagatcaacttcaacacccg ctttgtcatg aagacgctca tgaccatctg 180 ccctggcact gtgctgctcgtgttcagcat ctctctgtgg atcattgctg cctggaccgt 240 ccgtgtctgt gaaagtcctgaatcaccagc ccagccttct ggctcatcac ttcctgcttg 300 gtaccatgac cagcaggacgtaactagtaa ctttctgggt gccatgtggc tcatctccat 360 cacattcctt tccattggttatggggacat ggtgccccac acatactgtg ggaaaggtgt 420 ctgtctcctc actggcatcatgggtgcagg ctgcactgcc cttgtggtgg ccgtggtggc 480 ccgaaagctg gaactcaccaaagcggagaa gcacgttcat aacttcatga tggacactca 540 gctcaccaag cggatcaagaatgctgcagc caatgtcctt cgggaaacat ggttaatcta 600 taaacacaca aagctgctaaagaagattga ccatgccaaa gtgaggaaac accagaggaa 660 gttcctccca agctatccaccagtttgagg agcgtcccag atggaacaga ggaaagctga 720 gtgaccaagc caacactctggtggaccttt ccaagatgca gaatgtcatg tatgacttaa 780 tcacagaact caatgaccggagcgaagacc tggagaagca gattggcagc ctggagtcga 840 agctggagca tctcaccgccagcttcaact ccctgccgct gctcatcgcc gacaccctgc 900 gccagcagca gcagcagctcctgtctgcca tcatcgaggc ccggggtgtc agcgtggcag 960 tgggcaccac ccacaccccaatctccgata gccccattgg ggtcagctcc acctccttcc 1020 cgaccccgtn cacaagttcaagcagttgct aaataaatct ccccactcca gaagcattaa 1080 aaaaaaaaaa aaaaaaaaa1099 28 941 DNA Homo sapiens misc_feature (864) n equals a,t,g, or c 28aattcggcag agagccaacc gagggcgttc ctgtcggggc tgcagcggcg ggagggagcc 60cagtggaggc gccctcccga agcgccactg cccatgctga ccacccagcc ctccggctgc 120tgatgtcatg agtaacacca ctgtgcccaa tgccccccag gccaacagcg actccatggt 180gggctatgtg ttggggccct tcttcctcat caccctggtc ggggtggtgg tggctgtggt 240aatgtatgta cagaagaaaa agcgggtgga ccggctgcgc catcacctgc tccccatgta 300cagctatgac ccagctgagg aactgcatga ggctgagcag gagctgctct ctgacatggg 360agaccccaag gtggtacatg gctggcagag tggctaccag cacaagcgga tgccactgct 420ggatgtcaag acgtgacctg acccccttgc cccacccttc agagcctggg gtyctggact 480gcctggggcc ctgccatctg cttcccctgc tgtcacctgg stccccctgc tgggtgctgg 540gtctccattt ctccctccac ccaccctcag cagcatctgc ttcccatgcc ctcaccatca 600cctcactgcc cccaggcctt ctgccctttg tgggtgttga gctcaccgcc cacccacagg 660cactcatggg aagaggcttt ccttctggga tggcggcggc tggtagacac ctttgctttc 720tctagccctc ctgggctggg cttgggcaca aatccccagg caggctttgg agttgtttcc 780atggtgatgg ggccagatgt atagtattca gtatatattt tgtaaataaa atgttttgtg 840gctaaaaaaa aaaaaaaaaa atcnaagggg gggccggtac ccaaattccc cctatantga 900attcgtatta acaattcact tggggccgtc cttttaanaa c 941 29 756 DNA Homosapiens 29 ggcacgagga agctggagcg ggccggcggt gcagtcacgg gggagcgaggcctgctgggc 60 ttggcaacga gggactcggc ctcggaggcg acccagacca cacagacactgggtcaagga 120 gtaagcagag gataaacaac tggaaggaga gcaagcacaa agtcatcatggcttcagcgt 180 ctgctcgtgg aaaccaagat aaagatgccc attttccacc accaagcaagcagagcctgt 240 tgttttgtcc aaaatcaaaa ctgcacatcc acagagcaga gatctcaaagattatgcgag 300 aatgtcagga agaaagtttc tggaagagag ctctgccttt ttctcttgtaagcatgcttg 360 tcacccaggg actagtctac caaggttatt tggcagctaa ttctagatttggatcattgc 420 ccaaagttgc acttgctggt ctcttgggat ttggccttgg aaaggtatcatacataggag 480 tatgccagag taaattccat ttttttgaag atcagctccg tggggctggttttggtccac 540 agcataacag gcactgcctc cttacctgtg aggaatgcaa aataaagcatggattaagtg 600 agaagggaga ctctcagcct tcagcttcct aaattctgtg tctgtgactttcgaagtttt 660 ttaaacctct gaatttgtac acatttaaaa tttcaagtgt actttaaaataaaatacttc 720 taatggaaaa aaaaaaaaaa aaaaaaaaaa actcga 756 30 2100 DNAHomo sapiens misc_feature (1) n equals a,t,g, or c 30 nccagaggcagaaagtcctg cttctggggc gtaacctaca ggatatcctt ggaacagaag 60 atcttattgtggaagtract tccaatgatg ctgtgagatt ttatccctgg accattgata 120 ataaatactattcagcagac atcaatctat gtgtggtgcc aaacaaattt cttgttactg 180 cagagattgcagaatctgtc caagcatttg tggtttactt tgacagcaca caaaaatcgg 240 gccttgatagtgtctcctca tggcttccac tggcaaaagc atggttaccy gaggtgatga 300 tcttggtctgcgatagagtg tctgaagatg gtataaaccg acaaaaagct caagaatggt 360 gcatccaaacatggctttga attggtagaa cttagtccag aggagttgcc tgaggaggat 420 gatgacttcccagaatctac aggagtaaag cgaattgtcc aagccctgaa tgccaatgtg 480 tggtccaatgtagtgatgaa gaatgatagg aaccaaggct ttagcttgct gcaactcatt 540 gactggaacaaaccatagca ttgggtcagc agatccctgt cacccagagc aaccccattt 600 gccagcagcagatagtactg aatccctctc tgatcatcgg ggtggtgcat ctaacacaac 660 agatgcccaggttgatagca ttgtggatcc catgttagat ctggatattc aagaattagc 720 cagtcttaccactggaggag gagatgtgga gaattttgaa agactctttt caaagttaaa 780 ggaaatgaaagacaaggctg cgacgcttcc tcatgagcaa agaaaagtgc atgcagaaaa 840 ggtggccaaagcattctgga tggcaatcgg gggagacaga gatgaaattg aaggcctttc 900 atctgatgaagagcactgaa ttattcatac tagggtttga ccaacaaaga tgctagctgt 960 ctctgagatacctctctact cagcccagtc atattttgcc aaaattgccc ttatcatgtt 1020 ggctgcctgacttgtttata gggtcccctt aattttagtt tttagtagga ggttaaggag 1080 aaatcttttttttcctcagt atattgtaag agagtgagga atacagtgat agtaatgagt 1140 gaggatttcttaaatrtact ttttttttgt tctaggaatg agggtaggat aaatctcaga 1200 ggtctgtgtgatttactcaa gttgaagaca acctccaggc cattcctggt caacctttta 1260 agtagcatttccagcattca cacttgatac tgcacatcag gagttgtgtc acctttcctg 1320 ggtgatttgggttttctcca ttcaaggagc ttgtagctct gaagctatga tgcttttatt 1380 gggaggaaaggaggcagctg cagaattgat gtgagctatg tggggccgaa gtctcagccc 1440 gcagctaagtctctacctaa gaaaatgcct ctgggcattc ttttgaagta tagtgtctga 1500 gctcatgctagaaagaatca aaaagccagt gtggattttt agactgtaat aaatgaggca 1560 aaggatttctattccagtgg gaagraaacc tctctactga gttgtggggg atatgttgta 1620 tgttagagagaaccttaagg agtccttgta tgggccatgg agacagtatg tgataacata 1680 ccgtgattttcatgaagaaa ttcttctgtc ttagagttct cccctgctgc ttgagatgcc 1740 agagctgtgttgttgcacac ctgcaaaaca aggcacattt ccccctttct ctttaaagcc 1800 aaagagagatcactgccaaa gtgggagcac taaggggtgg gtggggaagt gaaatgttag 1860 gcgatgaattcctgagcacc ttgtttttct tccaaggttc gtagctcctc tctgcccttc 1920 caagcctgtaacctcggagg actatctttt gttctttatc ctttgtcttg tttgagtggg 1980 tcagccccagaggaactgat aagcaaatgg caagttttta aaggaagagt ggaaagtact 2040 gcaaataaaaatccttattt gtttttgtag aaaaaaaaaa aaaaaaaaaa aaaaaaaaag 2100 31 1448 DNAHomo sapiens 31 aaaaaaaaaa aaagcccacc tgaaagcctg tctctttcca ctttgttggcccttccagtg 60 ggattatcga gcatgttgtt ttttcatagt gcctttttcc ttatttcaagggttgcttct 120 gagtggtgtt tttttttttt ttaatttgtt ttgttttaaa ataagttaaagacagtccag 180 agcttttcag ccaatttgtc tcctactctg tgtaaatatt tttccctccgggcaggggag 240 ccagggtaga gcaaaggaga caagcaggag tggaaggtga ggcgttctcctgcttgtact 300 aagccaggag stttaagctc cagctttaag ggttgtgagc cccttggggttcagggaact 360 gcttgcccag ggtgcagtgt gagtgtgatg ggccaccggg gcaagagggaaggtgaccgc 420 ccagctctcc cacatcccac tggatctggc ttacaggggg gtcggaagcctgtcctcacc 480 gtctcggggg ttgtggcccc cgccccctcc ctatatgcac ccctggaaccagcaagtccc 540 agacaaggag agcggaggag gaagtcatgg gaacgcagcc tccagttgtagcaggtttca 600 ctattcctat gctggggtac acagtgagag tactcacttt tcacttgtcttgctcttaga 660 ttgggccatg gctttcatcc tgtgtcccct gacctgtcca ggtgagtgtgagggcagcac 720 tgggaagctg gagtgctgct tgtgcctccc ttcccagtgg gctgtgttgactgctgctcc 780 ccacccctac cgatggtccc aggaagcagg gagagttggg gaaggcaagattggaaagac 840 aggaagacca aggcctcggc agaactctct gtcttctctc cacttctggtcccctgtggt 900 gatgtgcctg taatcttttt ctccacccaa accccttccc acgacaaaaacaagactgcc 960 tccctctctt ccgggagctg gtgacagcct tgggcctttc agtcccaaagcggccgatgg 1020 gagtctccct ccgactccag atatgaacag ggcccaggcc tggagcgtttgctgtgccag 1080 gaggcggcag ctcttctggg cagagcctgt ccccgccttc cctcactcttcctcatcctg 1140 cttctctttt cctcgcagat gataaaagga atctggcatt ctacacctggaccatttgat 1200 tgttttattt tggaattggt gtatatcatg aagccttgct gaactaagttttgtgtgtat 1260 atatttaaaa aaaaaatcag tgtttaaata aagacctatg tacttaatcctttaactctg 1320 cggatagcat ttggtaggta gtgattaact gtgaataata aatacacaatgaattcttma 1380 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaccccggg gggggccccgggccccaatt 1440 ccccccaa 1448 32 456 DNA Homo sapiens misc_feature (444)n equals a,t,g, or c 32 ggcacagcaa acttgacgcc atgaagatcc cggtccttcctgccgtggtg ctcctctccc 60 tcctggtgct ccactctgcc cagggagcca ccctgggtggtcctgaggaa gaaagcacca 120 ttgagaatta tgcgtcacga cccgaggcct ttaacaccccgttcctgaac atcgacaaat 180 tgcgatctgc gtttaaggct gatgagttcc tgaactggcacgccctcttt gagtctatca 240 aaaggaaact tcctttcctc aactgggatg cctttcctaagctgaaagga ctgaggagcg 300 caactcctga tgcccagtga ccatgacctc cactggaagagggggctagc gtgagcgctg 360 attctcaacc taccataact ctttcctgcc tcaggaactccaataaaaca ttttccatcc 420 aaaaaaaaaa aaaaaaaaac cccngggggg gcccgg 456 331326 DNA Homo sapiens misc_feature (352) n equals a,t,g, or c 33ggcacgagtg caggcccaga gaggactcat tgaaaggact gaaaggggag gtggcgtttt 60cttcctaccc aaacttaccc ctgtgagctg gacagcttgg tagcacctgc ctggacttag 120atggtggtag ccaagaagac tgacatttta gggaacagga cggggaggag aaggctctgg 180cacacacaca tgtgtccata tgtcctgcaa tggtctgggg actattgcta ggctaggagc 240cctaagtgtc ttcttcctca tgtctmttct cccctgtstc atgggcccta agrtctcttt 300cactgggcct gcctcaatga acgtgctgcc cagctacccc gaaacacggc anctgccggc 360tatcaatgcc ccagctgcaa tggcccatct tcccccaacc aacctggctg ggcccgtggg 420ctccgcactg agararaaas ttggcacart caactgggcc cgggcaggac tgggccyccc 480tctgatcgat gaagktggtg arcccagagc ccgagcccct caacacgtct gacttctctg 540actggtctag ttttaatgcc agcagtaccc ctggaccaga ggaggtagac agcgcctctg 600ctgccccagc cttctacagc cgagcccccc ggcccccagc ttccccaggc cggcccgagc 660agcacacagt gatccacatg ggcaatcctg agcccttgac tcacgcccct aggaaggtgt 720atgatacgcg ggatgatgac cggacaccag gcctccatgg agactgtgac gatgacaagt 780accgacgtcg gccggccttg ggttggctgg cccggctgct aaggagccgg gctgggtctc 840ggaagcgrcc gctgaccctg ctccagcggg cggggctgct gctactcttg ggactgctgg 900gcttcctggc cctccttgcc ctcatgtctc gcctaggccg ggccgcagct gacagcgatc 960ccaacctgga cccactcatg aaccctcaca tccgcgtggg cccctcctga gcccccttgc 1020ttgtggctag gccagcctag gatgtgggtt ctgtggagga gaggcggggt aatggggagg 1080ctgagggcac ctcttcactg cccctctccc tcaagcctaa gacactaaga ccccagaccc 1140aaagccaagt ccaccagagt ggctgcaggc caggcctgga gtccccgtgg gtcaagcatt 1200tgtcttgact tgctttcctc ccgggtytcc agcctccgac ccctcgcccc atgaaggagc 1260tggcaggtgg aaataaacaa caactttatt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1320aaanaa 1326 34 710 DNA Homo sapiens 34 gcgaaagaga aaaaggctgg agctcccgcccccggggctg tcagatggct tgggtttctg 60 cgacgcgatt ggctcgcgga gggcagaaattactcagcaa acatgactat tattagctgc 120 ttagcaacag ctcaccaaag tagagagaccacccaggtag gcaacccagt gtgtgcatcc 180 tcggcttcgg ggcagcctct gagagcgccaaccttctcgc atgcaatact tccattaagg 240 aatgctcccc ctcctttctc tcttattccttttcttttca acagtgtctt ctttttgtgg 300 gatgcctttg cgcgcacaca cgcgcgcgcasgcacacaca cgaacatttg cctcgcggta 360 gacacggggg gaaatgtwat atttttttaagcgcttaaac aatttctgaa attcctcaaa 420 gaaaagcctt tcagargcac cttggcctcaagctgcaaca aatactggga rgtccggctc 480 gcattcccag gcctgcacca ataatgacagcgtgctggat artgcgccag tgtgtgccag 540 attttttttt cctcttctct tttcttttataactaaaggg aagacttagg ctcttgcagg 600 gaacaacgcc tcgcattaag ataaacagaatggaaagtta aagaggaaag caaggacgtt 660 gggaaaagcc atctttctta aaatccgtctgccccccagc cgctttctcc 710 35 1188 DNA Homo sapiens 35 gatggcttttatatctatta tcgacccaca gacagtgaca atgatagtga ctacaagaag 60 gatatggtggaaggggacaa gtactggcac tccatcagcc acctgcagcc agagacctcc 120 tacgacattaagatgcagtg cttcaatgaa ggaggggaga gcgagttcag caacgtgatg 180 atctgtgagaccaaagctcg gaagtcttct ggccagcctg gtcgactgcc acccccaact 240 ctggccccaccacagccgcc ccttcctgaa accatagagc ggccggtggg cactggggcc 300 atggtggctcgctccagcga cctgccctat ctgattgtcg gggtcgtcct gggctccatc 360 gttctcatcatcgtcacctt catccccttc tgcttgtgga gggcctggtc taagcaaaaa 420 catacaacagacctgggttt tcctcgaagt gcccttccac cctcctgccc gtatactatg 480 gtgccattgggaggactccc aggccaccag gcagtggaca gccctacctc agtggcatca 540 gtggacgggcctgtgctaat gggatccaca tgaatagggg ctgcccctcg gctgcagtgg 600 gctacccgggcatgaagccc cagcagcact gcccaggcga gcttcagcag cagagtgaca 660 ccagcagcctgctgaggcag acccatcttg gcaatggata tgacccccaa agtcaccaga 720 tcacgaggggtcccaagtct agcccggacg agggctcttt cttatacaca ctgcccgacg 780 actccactcaccagctgctg cagccccatc acgactgctg ccaacgccag gagcagcctg 840 ctgstgtgggccagtcaggg gtgaggagag cccccgacag tcctgtcctg gaagcagtgt 900 gggaccctccatttcactca gggcccccat gctgcttggg ccttgtgcca gttgaagagg 960 tggacagtcctgactcctgc caagtgagtg gaggagactg gtgtccccag caccccgtag 1020 gggcctacgtaggacaggaa cctggaatgc agctctcccc ggggccactg gtgcgtgtgt 1080 cttttgaaacaccacctctc acaatttagg cagaagctga tatcccagaa agactatata 1140 ttgttttttttttaaaaaaa aaaaaaaaaa awcycggggg ggggcccc 1188 36 956 DNA Homo sapiensmisc_feature (404) n equals a,t,g, or c 36 ggcagagcag tgaaaatgcatcctaaaaat tcaatgttta taccaggctc atgacactaa 60 gatgtgacat ctggacacgaggggtcagcc acgtggatac atccctccca gattgcatct 120 ccaggaatca ctctgctagcagaatgggcg ccccatccct tactatgctg ctcctcctca 180 aagtgcagcc cagaaggacccaggcctttg atgcacattg ggtgggtctc ccactacttt 240 agttgaaatg ggagcatgctggagtcggcg ttctgttgct tctggtgaga aggacatccc 300 attgacccct ggccaccaggtccagtattc catccttcct tctgtcccag cctatcgccc 360 tccccacyag gcccacccccacaacttctc ctcaagggag gttntcccgc agctggaggg 420 cttgcacaga ccagcagtcacagaaatcat tcttcctgct gtactgggcc ttaactgcct 480 gcaaatgtcc gagcactactgcataggatg ccagagccac cgaagataaa cacagccaag 540 tttaataata ataaaaggaaaaatctcagc ctgcagaact ctggttttga cccaccatcg 600 gccagatgca catcttcagggcctgttgag caccttctga aaagcagggc tcgtaataga 660 ctccagcaca ttccatcagagtcaggaaaa ctgcggtgag tcccagagaa tctagggtgc 720 agggcaggga gcaggagtcataaggagtga taacctaaac tgtgtgtagt cagcggggag 780 ggtcttatgt tatcaggtgaaatgagagcc agtaagttag ttgatcctgt cacagatata 840 accctgataa caccccatagatacgcgaca cgtgtgtcct gcccctgctt tccccatcca 900 acatggttct tctgttccacagacattaaa ggggctttct gcaattactt aaaaaa 956 37 1603 DNA Homo sapiens 37tcgacccacg cgtccgctct gccaggaatc tggtctttct gtagacccaa gtcagaaaga 60accatttgtg gagttaaatc gaatattaga rgcattaaar gtcagagttc tgagacctgc 120tctggaatgg gcagtttcaa accgagagat gcttatagcc caaaacagct ccttggaatt 180taaactacac agactgtatt ttattagctt rttaatgggt ggaacacaaa tcagcgagar 240gcattacaat atgctaaaaa ttttcagcca tttgccctaa atcatcaaaa agacattcag 300gttttgatgg gaagccttgt gtacctgaga caagggattg agaactcacc atatgttcac 360ctacttgatg caaaccagtg ggctgatatc tgtgacatct ttacacggga tgcttgtgcc 420ctcctggggc tctccgtgga gtcccctctc agtgtcagtt tctcagcagg ttgtgtggcg 480ctgccagctt taattaacat caaagccgtg attgaacaga ggcagtgtac tggagtttgg 540aaccagaaag atgaattacc tattgaagtg gaccttggta aaaagtgctg gtatcactct 600atatttgcct gccccattct tcgtcagcaa acaacagata acaatccacc catgaaattg 660gtctgtggtc atattatatc aagagatgcc ctgaataaaa tgtttaatgg tagcaaatta 720aaatgtccct actgtccaat ggaacaaagt ccaggagatg ccaaacagat atttttctga 780agagataact ttagtttgca atttgtaagt gaaactgaat cgtgggtgca tttcagaaga 840gaacgttcca tataatgcag ctaaccaagg actcctgtgt ttctataagc taatgctcca 900gaaactttgc caacctgtta gtgtacacac actgagggga gtgctcccgg tgaatattat 960catagggctt tattatattc ttggtcttca tttctgatca agtaaataca ccagcagttg 1020tcattcaatg caggtttttg tacttaatta tatggtgatt tttttacttt ttaagagcag 1080aaacggaaat tgacctcccc gccatgtgtt taatattcct cctgctttta cttttgtcat 1140tttcttgata atcgtaagcc ttgagagtgt ttgtgaaaaa gttttatttc ctgttatgta 1200tacataatta aatgaaaatt cttcagaaaa agtttgataa attgaattgt ggttatgaaa 1260ctaatttgca tttttatttg cttaagaaag aaagctgtga tagattccag atatgctttt 1320tgatgttttc ctctgctcca gctccaagaa gtcagcacac ctgcatttta gctctgcatg 1380cagccccagc aggctgcgtg tttaagaatt tcattgttta actggctggt gtgagaagtc 1440ttccgttagc atagagtgga aggagtacta ttgtttggtt gggtttttgt ttgtttgttt 1500tttgtttttg cttttattgc caagaggtgc ttgttttaaa agtatgttta ataaaatgaa 1560attctaaagt taaraagtgt tcttaaagtt gatatttaac tct 1603 38 1089 DNA Homosapiens 38 ggcacgagct acctttctgc ctgctttgct ggctgcaaca gcacgaatctcacgggctgt 60 gcgtgcctca ccaccgtccc tgctgagaac gcaaccgtgg ttcctggaaaatgccccagt 120 cctgggtgcc aagaggcctt cctcactttc ctctgtgtga tgtgtatctgcagcctgatc 180 ggtgccatgg caagacaccc tcagtcatca tcctcatcag gacagtcagccctgaactca 240 agtcttacgc tttgggagtt ctttttctcc tccttcgttt gttgggcttcatccctccac 300 ccctcatctt cggggctggc atcgactcca cctgcctgtt ctggagcacgttctgtgggg 360 agcaaggcgc ctgcgtcctc tacgacaatg tggtctaccg atacctgtatgtcagcatcg 420 ccatcgcgct caaatccttc gccttcatcc tgtacaccac cacgtggcagtgctgaggaa 480 aaactataaa cgctacatca aaaaccacga gggcgggctg agcaccagtgagttctttgc 540 ctctactctg accctagaca acctggggag ggaccctgtg cccgcaaaccagacacatag 600 gacaaagttt atctataacc tggaagacca tgagtggtgt gaaaacatggagtccgtttt 660 atagtgacta aaggagggct gaactctgta ttagtaatcc aagggtcatttttttcttaa 720 aaaaagaaaa aaaggttcca aaaaaaacca aaactcagta cacacacacaggcacagatg 780 cacacacacg cagacagaca caccgacttt gtcctttttc tcagcatcagagccagacag 840 gattcagaat aaggagagaa tgacatcgtg cggcagggtc ctggaggccactcgcgcggc 900 tgggccacag agtctacttt gaaggcacct catggttttc aggatgctgacagctgcaag 960 caacaggcac tgccaaattc agggaacagt ggtggccagc ttggaggatggacatttctg 1020 gatacacata cacatacaaa acagaaaaca ttttttaaaa gaagtttcctaaaataaaaa 1080 aaaaaaaaa 1089 39 629 DNA Homo sapiens 39 agctcagttcccttagaaat gaaattttaa atgacactac caggtaagcc actgagacca 60 gtggaggtgatagctaagaa cataaggaat taagaatttt taatggagaa aggaggtaat 120 gaataccagttacatcctaa gactcactgt agtggtgagt gttgtaattt atctcgctat 180 ccatcctcttttaagttttt ccttagaaag tcctctattg gtaccttgga gggactgctg 240 tcaaaatatatggaaaagtg ggtctgtgtg gtacaagagg tggactttgc cacacatgga 300 agtttgctgccaagatcttc actaatgaaa gaaatcacca gtgagctgca cagattagcc 360 aaatactgagctcattagaa ctactaaggc ctggacattt ctgcctaatc caggactcct 420 gtaattatcagtctttgctt tggagcttcc cattgtgtag ctgaraattt gtcatatctg 480 cattataatctaaggctcca catacttaat cctgcttctc cccctttttc tttccctttc 540 ccagcggtcagctctgctgc atagtctgaa gactttccct gcccaatcct gataaaattc 600 ttgcactcgtaaccccatct cagtgtctg 629 40 1964 DNA Homo sapiens misc_feature (353) nequals a,t,g, or c 40 aagaagacat ggaaattgct gaaggatgtt tcaggcatattaagaaaatc tttacgcagc 60 ttgaggaatt cagagcctct gaattgcttc gaagtggactggacagatct aaataccttt 120 tagtgaaaga agccaaaatt attgctatga cctgtactcatgctgcctta aaacgacatg 180 acttggtcaa gctaggtttc aagtatgaca acattttgatggaagaggct gctcagattc 240 tggagataga aacttttatc cctcttcttc tacagaatcctcaggatgga tttagccgac 300 taaaacgatg gattatgatt ggcgatcatc accagttacctccagttatt aangaacatg 360 gcctttcaaa agtactcaaa catggagcag tctctcttcactcgctttgt tcgcgttgga 420 gttccgactg ttgaccttga tgctcaaggg agagccagagcaagcttgtg camctnctac 480 aactggcgat acaagaatct aggaaactta ccccatgtgcagctcttgcc agagtttagt 540 acagcaaatg ctggcttact gtatgacttc cagctcattaatgttgaaga ttttcaagga 600 gtgggagaat ctgaacctaa tccttacttc tatcagaatcttggagaggc agaatatgta 660 gtagcacttt ttatgtacat gtgtttactt ggttaccctgctgacaaaat cagtattcta 720 acaacatata atggccaaaa gcatcttatt cgcgacatcatcaatagacg atgtggaaac 780 aatccattga ttggaagacc aaacaaggtg acaactgttgatagatttca aggtcaacag 840 aatgactata ttcttctttc tctggtacga accagggcagtgggccatct gagggatgtc 900 cgtcgcttgg tagtggccat gtctagagcc agacttggactttatatctt cgccagagta 960 tccctcttcc aaaactgttt tgaactgact ccagctttcagtcagctcac agctcgcccc 1020 cttcatttgc atataattcc aacagaacct ttcccaactactagaaagaa tggagagaga 1080 ccatctcatg aagtacaaat aataaaaaat atgccccagatggcaaactt tgtatacaac 1140 atgtacatgc atttgataca gactacacat cattatcatcagactttatt acaactacca 1200 cctgctatgg tagaagaggg tgaggaagtt caaaatcaagaaacagaatt ggaaacagaa 1260 gaagaggcca tgactgttca agctgacatc atacccagtccaacagacac cagctgccgt 1320 caagaaactc cagcctttca aactgacacc acccccagtgagacaggagc cacttccact 1380 ccagaagcca tccctgcttt atctgagacc acccctactgtggtaggagc tgtatctgca 1440 ccggcagaag ctaacacacc tcaggatgcc acatctgccccagaagagac caagtagcca 1500 aactgtagtc cttctaaagg aggacatggc agtcaaaaagtctgagtaaa gctgtttttt 1560 gtattttata tttgcttctg ccattttact gtcactaattaatgtttagt tcttatattt 1620 gttaactgat ttcggtgtct tgaatatatt tttttaaattatgtgtatga acaattctag 1680 tttcatttgt tcaatcagaa gagcaaataa ccattcctttcatgttttga tcactgagtg 1740 tgtctgtaat catacctaca ttaaaatcat tttctatgaatatataatat atacttcaca 1800 tttttagtga acttctctaa agaagaggac agaatatactggacttaacc acgaataccc 1860 ttgagtgtcc aaattgggaa ggaactkgtt tcttcygttatactaycaaa tgcttaaatt 1920 ckgtttcctt ttttcttacc tttgtttgct gtctttatgtaaag 1964 41 1522 DNA Homo sapiens misc_feature (1282) n equals a,t,g,or c 41 cgtgtccgcg cgcctgggag acgctgcctc ggcccggacg cgcccgcgcccccgcggctg 60 gagggtggtc gccactggga cactgtgaac caggagtrag tcggagctgccgcgctgccc 120 aggccatgga ctgtgaggtc aacaacggtt ccagcctcag ggatgagtgcatcacaaacc 180 tactggtgtt tggcttcctc caaagctgtt ctgacaacag cttccgcagagagctggacg 240 cactgggcca cgagctgcca gtgctggctc cccagtggga gggctacgatgagctgcaga 300 ctgatggcaa ccgcagcagc cactcccgct tgggaagaat agaggcagattctgaaagtc 360 aagaagacat catccggaat attgccaggc acctcgccca ggtcggggacagcatggacc 420 gtagcatccc tccgggcctg gtgaacggcc tggccctgca gctcaggaacaccagccggt 480 cggaggagga ccggaacagg gacctggcca ctgccctgga gcagctgctgcaggcctacc 540 ctagagacat ggagaaggag aagaccatgc tggtgctggc cctgctgctggccaagaagg 600 tggccagtca cacgccgtcc ttgctccgtg atgtctttca cacaacagtgaattttatta 660 accagaacct acgcacctac gtgaggagct tagccagaaa tgggatggactgaacggaca 720 gttccagaag tgtgactggc taaagctcga tgtggtcaca gctgtatagctgcttccagt 780 gtagacggag ccctggcatg tcaacagcgt tcctagagaa gacaggctggaagatagctg 840 tgacttctat tttaaagaca atgttaaact tataacccac tttaaaatatctacattaat 900 atacttgaat gaaaatgtcc atttacacgt atttgaatgg ccttcatatcatccacacat 960 gaatctgcac atctgtaaat ctacacacgg tgcctttatt tccactgtgcaggttcccac 1020 ttaaaaatta aattggaaag caggtttcaa ggaagtagaa acaaaatacaatttttttgg 1080 taaaaaaaaa ttactgttta ttaaagtaca accatagagg atggtcttacagcaggcagt 1140 atcctgtttg aggaaagcaa gaatcagaga aggaacatac cccttacaaatgaaaaattc 1200 cactcaaaat agggactatc yatcttaata ctaaggaacc aacaatcttcctgtttaaaa 1260 aaccacatgg cacagagatt cngaactaaa gtgctgcact caaatgatgggaagtcccgg 1320 ccccagtaca ccaggggctt tggacttttt tcaacttcgt ttccttttgtttggantcca 1380 aaagaaccac tttgtggttc ttaaaagggt gtgaaggtga tttaaggggcccaggtcagc 1440 cactggttgg tttacaaaat cngggtaact aactgcatac aactttttcccntttccatg 1500 ncatcaggac tttgctaaag ac 1522 42 875 DNA Homo sapiens 42tgggatttcc ctttatcatg gaggccttgt cccacttcct ctatgtccct ttccttggtg 60tctgtgtctg tggggccatc tacactggcc tgttccttcc tgagaccaaa ggcaagacct 120tccaagagat ctccgaggaa ttacacagac tcaacttccc caggcgggcc cagggcccca 180cgtggaggag cctggaggtt atccagtcaa cagaactcta gtcccaaagg ggtggccgta 240gccaaagcca gctaccgtcc tgtcctctgc ttcctgccag ggccctggtc ctcamtycct 300yctgcattcc tcatttaagg agtgtttatt gagcaccctt tgtgtgcaga catggctcca 360ggtgcttagc aatcawtggt gagcgtggta tccaggctaa aggtaattaa ctgacagraa 420atcagtaaca acataattac aggytggttg tggcagytca tgactgtaat cccagcactt 480ttgggagcca aggtgggarg atcaattgag gccagagttt gaaamcagct aggtaacata 540gtgagacccc ctatctctac aaaaaatttt aaacattagc tgggcatggt ggtatgtgct 600aacagctcta gctactcagg aggctgaggc agcaggatca cttgagtcca agagttcaag 660gtagcagtaa gctacaatca caccactgca tgccagactg ggtgacagag ggagacttca 720tctctttaaa acataataat aataattaca gactcaggaa atgcagtgaa agaaaaatac 780aggttggcca ggtgaggtgg ctgatgcctg taatcccagc actttgggag gccaagatgg 840gaagattgct ttgagaccag aagtttgaga ccagc 875 43 843 DNA Homo sapiensmisc_feature (14) n equals a,t,g, or c 43 cccacgcggt ccgnatcgtccttccctcac ttcagagggt ggccagagct gaatacccag 60 agagggacaa gtaagggtccagttccaaaa catcatgagg atgtatcatc ccacgtgtct 120 cacctgacag ttacagaggaaacccgcacc cagaatgcac gtgctgtctt atgggaacac 180 tcagcgcaga gtgctcaggtccggccacac tcgggctgtg cttggtcgtg ccatggaatt 240 cctcaggact ttctcagcctccctaatggc agaagcccct ttacagcaag acatttaccg 300 tttgtctgaa aatagccgaactgagctttt cttcaggcta tatgagaagt ctctagacag 360 tgggcaccgt cagaaagcccagagccttgt gatagctccc accctgcctg gctcagatct 420 tcccattttt tttcctctggcactaacctc accttttgtt tttttgtgtt tgtgtttgtt 480 tttgtttttg cagagttggattacagaaac tcctatgaaa ttgaatatat ggagaaaatt 540 ggctcctcct tacctgtaagttcgtctgcc tcgggccact taggggactc gctttcctgc 600 cttcaggggc ctcctcccctgtgcagagtg tctctgggag ctcagacccc aaatcgagtg 660 ttttctgtgt acacagcttcccgggtgcac agcaatgatg gactggggct ggggggttga 720 ggtttgtact caatccacttcgtttgacat tttcagggag aaaatgatag aatacaatta 780 gacgtcctgc agaattactttcctagactg agaaagagct agagatttct ttaaaaaaaa 840 aaa 843 44 489 DNA Homosapiens 44 ctcttaggct ttgaagcatt tttgtctgtg ctccctgatc ttcaggtcaccaccatgaag 60 ttcttagcag tcctggtact cttgggagtt tccatctttc tggtctctgcccagaatccg 120 acaacagctg ctccagctga cacgtatcca gctactggtc ctgctgatgatgaagcccct 180 gatgctgaaa ccactgctgc tgcaaccact gcgaccactg ctgctcctaccactgcaacc 240 accgctgctt ctaccactgc tcgtaaagac attccagttt tacccaaatgggttggggat 300 ctcccgaatg gtagagtgtg tccctgagat ggaatcagct tgagtcttctgcaattggtc 360 acaactattc atgcttcctg tgatttcatc caactactta ccttgcctacgatatcccct 420 ttatctctaa tcagtttatt ttctttcaaa taaaaaataa ctatgagcaacaaaaaaaaa 480 aaaaaaaaa 489 45 534 DNA Homo sapiens misc_feature (470)n equals a,t,g, or c 45 gaagcagtgt gtatctatga ttatatctct gttcatctatatatttttga catgtagcaa 60 cacctctcca tcttatcaag gaactcaact cggtctgggtctccccagtg cccagtggtg 120 gcctttgaca ggtaggagga tgcagtgctg caggctattttgttttttgt tacaaaactg 180 tcttttccct tttcccctcc acctgattca gcatgatccctgtgagctgg ttctcacaat 240 ctcctgggac tgggctgagg caggggcttc gctctattctccctaaccat actgtcttcc 300 tttccccttg ccacttagca gttatccccc cagctatgccttctccctcc ctcccttgcc 360 ctggcatata ttgtgcctta tttatgctgc aaatataacattaaactatc aagtgaaaaa 420 aaaaaaaaaa aaaactccaa gggggggccg gtacccaattccccctatan tgagtcntat 480 tacaattcac tgggccgtcg ttttacaacg tcgtgaatgggaaaacctgg gcgt 534 46 1374 DNA Homo sapiens 46 ggcacgagtc cgggatgagctcagccgcgg ccgaccactg ggcgtggttg ctggtgctca 60 gcttcgtgtt tggatgcaatgttcttagga tcctcctccc gtccttctca tccttcatgt 120 ccagggtgct gcagaaggacgcggagcagg agtcacagat gagagcggag atccaggaca 180 tgaagcagga gctctccacagtcaacatga tggacgagtt tgccagatat gccaggctgg 240 aaagaaagat caacaagatgacggataagc tcaaaaccca tgtgaaagct cggacagctc 300 aattagccaa gataaaatgggtgataagtg tcgctttcta cgtattgcag gctgccctga 360 tgatctcact catttggaagtattattctg tccctgtggc tgtcgtgccg agtaaatgga 420 taacccctct agaccgcctggtagcctttc ctactagagt agcaggtggt gttggaatta 480 cctgttggat tttagtctgtaacaaagttg tcgctattgt gcttcatccg ttcagctgaa 540 caggaggatg gatacagccgcgaggctaaa aaacggattt cctcttccta gcttaaaatc 600 tgatttacac tgttttgttttttaagaaac aaaagtgcat agtttagatt tttttttttg 660 ttgaatatgt ttgttcttggactttatgag agagtcttat aagaatcacg attttctaca 720 cctgtcattg agccaagaaagtccagttta tgacacgtat gtactagtga acaccgtcct 780 cgatctgtac gaaatgtgaaatgtttaggg acatctccat gctgtcactt gtgatttgcc 840 ctcttatgta ttttggtcatattgccaact ggaaagtcaa aattttctaa caactttaag 900 taagttcttt gaagacttagtgctgttttt aatccagttt agaaagtaac ttaattttaa 960 taccactact aaaaattcgaaaatttcttc tttaatcaca ttcaatatgg ttaaaagaac 1020 aacactaatt gacattgcgtgggctttttc tccctttgtt taaaatgtca tttgttgagc 1080 aagagttgta tagtattatctacttacttg aggctgttaa tttttcatta cagtgttttg 1140 taaatgtatc cacgagaccatgatgcattg ttttgtgctc aacttgtgtt ttgtatttaa 1200 agcattttga atgaagtgtattttataagc atttaatatt tatgctcttt agaatggaac 1260 acagaaaaca aaccttataagtcctgatta atctgaacca ataacctgtg tggcctacaa 1320 agtataattc tattaaatgttccttaaaac aaaaaaaaaa aaaaaaaaaa aaaa 1374 47 596 DNA Homo sapiensmisc_feature (8) n equals a,t,g, or c 47 gaattcgnca cgagattacttggacatgaa agaactcagg ttcaagttta ttcatttact 60 aagttagtta aatcatgtgccttccatgag ccttcatttg gtaacttgga aaatggaaat 120 aataacacta gtcatatatattctacactg ctaccatatg gaccaaaggg attatagatt 180 acaatcacca tcattcctgctgacaggtat atagaaaaca atttcattga agaaaagtcc 240 ttacatttat ccttttcctaatatctgcat gggtaaacta ataaatatag tcattagaaa 300 acccttatta ttattattagttcaatgtga gaactgctgc agaaaaaata tgctttataa 360 tattttcttg aatatacataatattcataa attttcaaat cattgaaaat taccttaaaa 420 ttggaaaaaa tgtgcatttctactcatata acagtataaa attcctatgt caatctcttt 480 tttttttttt tgttttgagttggagtctcg ctctgtcgcc caggctgggc aacagagcag 540 gaccctgtct taattaaaaaaaaaaaaaaa aaactcgagg ggggcccggt acccta 596 48 851 DNA Homo sapiens 48cacatgaaga cacacagtgg tgagaagccc ttccgctgcg cccgctgtcc ttatgcctct 60cctcatctgg ataacctgaa acggcaccag cgcgtccata caggagagaa gccctacaag 120tgccccctct gcccttatgc ctgtggcaat ctggccaacc tcaagcgtca tggtcgcatc 180cactctggtg acaaaccttt tcggtgtagc ctttgcaact acagctgcaa ccagagcatg 240aacctcaaac gtcacatgct gcggcacaca ggcgagaagc cttccgctgt gccacctgcg 300cctataccac gggccactgg gacaactaca agcgccacca gaaggtgcat ggccacggtg 360gggcaggagg gcctggtctc tctgcctctg agggctgggc cccacctcat agcccaccct 420ctgttttgag ctctcggggc ccaccagccc tggggactgc tggcagccgg gctgtccaca 480cagactcatc ctgaactagg tccttcttcc ccatgtttta tacagacgga ccagaagcca 540cctttttctc ccccgctggc caggggctcc acacagacta acgtaggcac tataaggacc 600agcccaaccc catgggcggg ggggcccata tggaccaggg gaccttgcct tgactgaggc 660acttcacgag ctcagtgaga agggccctgt attcacctcc actgccccca ggggctgtgg 720acaaaccggc tgggggactg cccagcctcc cacctgttta tttaacttat ttcagtgctt 780tataataaag gaaacactaa caaagccatg tctatgctga attggcaatg gcaggcaatt 840tggccttacc c 851 49 2020 DNA Homo sapiens misc_feature (1239) n equalsa,t,g, or c 49 gtgaaatgaa aacagtcttt ttatagcctt tagcttgtga gtttggaagtttggggggtc 60 ttatgtttgt tttgcctctt ctgtttcttg gaggagagtt gaggcttttcttaggtgcat 120 acacagaccc aggtgaacac gctgactgtg aacctgccct gtatccggagctgtgctggg 180 cactgagggg atgcaacaaa attaggagag gwtccttgct cccaacgtctacttctccta 240 cctcaacagg ggtccagggt gcagtgaact cagttcttgg cccttgggtgaggattcatg 300 gatgaatgaa agctagacct gatggggagg cattatgact aaataggcccagcctccttc 360 ccttccagct ctgtcctagg agcataggcg ggaaatctga gtagagtctgactgcagttt 420 ttgcttatga tttgtaaaag ccgtcatggg gtcaataaga aaataggggtgatggagggg 480 gagaagccca ggactgggag aatcgcacgt gccccagggg ttttcaccaaggattttcaa 540 gacaaactgg agtaagaatt aaagccccag aggatttaat tatcctggtttgcaaaagag 600 cctcccatgc cagtaccgcc cagccttgga ggccggaatg ctcatggcccctgtggtctg 660 cttgtccttc agcccatgcc cagcagatac ctctctgact ggagacgggctcaaagctgg 720 attagaaagg ggagmggcac ttgtgacttt gtttgactct gtgactcacttcctcgctca 780 caccttgttt gaactactgg actttcaact ggctttcctt aggtcaggcaagcagacagc 840 tccccactga agaggtctgt acagtgacaa cccgggccgg cagcaaggacacagatgcag 900 ccacagtaag gctccatcag gactgggtca gtgatggcaa caggatggccaaggatggct 960 ctagaacayt ctgtccatgc gtcactcccc ccagttttrt ttttagctttggcttcaggg 1020 agtgacagcc atcacaaata gccacattct gctctactct ccaacataccagattstaca 1080 ctgttgttat ttcatgagac gtgaatgttg cagagagtgg ggggattctggttgttaagg 1140 aacttacact ggggagcttt actcttccgt gtcaacaatg tgactacatgttctccagat 1200 tagccacaca tgcaaacatc agtgtccttc tagctttanc cgagaaagaaaccagtccca 1260 gggaatgaat ggtggtctcc ccactcccgg cagcacttta ggcagcccataagctatgcg 1320 agaatgtgaa cgctcacctt gctccgtcac ggttctgacc taccacataaacaggaagaa 1380 gccagtgacc ggaacagctc taggaataac aagtcagaat agaagtgtcctttatattac 1440 cagaaaatat gggcttggcc taagtcgctg tctcctaacc tgccggggtcattccccacc 1500 aaacacccca tactaaggag ccatgagcca cctggacatt caccttttctttgaccatct 1560 ggagtctggg gcaacttaag gaaggcncca cacagtggtg caggcacatttccaagcgta 1620 ggtgtccctg gcttttgtgg ccaaagctag tgttatggtc aacaacaggccagggtctgt 1680 ggggcactga ccttgaaagt ggcaaaatgg aggtttcaca ggctgtgcgggagcaggacg 1740 gcttgcttca tctaacaatc tcagtttcct ttaaaaaaag aaagaaaggaaaagatttca 1800 taagcaggtg tcagtggaca gtttaagyac ttaaccattt ctctttcttcttatggatgt 1860 gaactgtgct gtggataaat catttgtatt tcttgaatgt tctctatgactaacagttat 1920 taagtcggtt gtgtatatgt gtaactaatg taactgcctt ttaaaatttcattacaataa 1980 aaatgacttt gctctgaama aaaaaaaaaa aaaaactcga 2020 50 2432DNA Homo sapiens 50 atgaagggtc gttggtggga aagatggcgg cgactctgggaccccttggg tcgtggcagc 60 agtggcggcg atgtttgtcg gctcgggatg ggtccaggatgttactcctt cttcttttgt 120 tggggtctgg gcaggggcca cagcaagtcg gggcgggtcaaacgttcgag tacttgaaac 180 gggagcactc gctgtcgaag ccctaccagg gtgtgggcacaggcagttcc tcactgtgga 240 atctgatggg caatgccatg gtgatgaccc agtatatccgccttacccca gatatgcaaa 300 gtaaacaggg tgccttgtgg aaccgggtgc catgtttcctgagagactgg gagttgcagg 360 tgcacttcaa aatccatgga caaggaaaga agaatctgcatggggatggc ttggcaatct 420 ggtacacaag gaatcggatg cagccagggc ctgtgtttggaaacatggac aaatttgtgg 480 ggctgggagt atttgtagac acctacccca atgaggagaagcagcaagag cgggtattcc 540 cctacatctc agccatggtg aacaacggct ccctcagctatgatcatgag cgggatgggc 600 ggcctacaga gctgggaggc tgcacagcca ttgtccgcaatcttcattac gacaccttcc 660 tggtgattcg ctacgtcaag aggcatttga cgataatgatggatattgat ggcaagcatg 720 agtggaggga ctgcattgaa gtgcccggag tccgcctgccccgcggctac tacttcggca 780 cctcctccat cactggggat ctctcagata atcatgatgtcatttccttg aagttgtttg 840 aactgacagt ggagagaacc ccagaagagg aaaagctccatcgagatgtg ttcttgccct 900 cagtggacaa tatgaagctg cctgagatga cagctccactgccgcccctg agtggcctgg 960 ccctcttcct catcgtcttt ttctccctgg tgttttctgtatttgccata gtcattggta 1020 tcatactcta caacaaatgg caggaacaga gccgaaagcgcttctactga gccctcctgc 1080 tgccaccact tttgtgactg tcacccatga ggtatggaaggagcaggcac tggcctgagc 1140 atgcagcctg gagagtgttc ttgtctctag cagctggttggggactatat tctgtcactg 1200 gagttttgaa tgcagggacc ccgcattccc atggttgtgcatggggacat ctaactctgg 1260 tctgggaagc cacccacccc agggcaatgc tgctgtgatgtgcctttccc tgcagtcctt 1320 ccatgtggga gcagaggtgt gaagagaatt tacgtggttgtgatgccaaa atcacagaac 1380 agaatttcat agcccaggct gccgtgttgt ttgactcagaaggcccttct acttcagttt 1440 tgaatccaca aagaattaaa aactggtaac accacaggctttctgaccat ccattcgttg 1500 ggttttgcat ttgacccaac cctctgccta cctgaggagctttctttgga aaccaggatg 1560 gaaacttctt ccctgcctta ccttcctttc actccattcattgtcctctc tgtgtgcaac 1620 ctgagctggg aaaggcattt ggatgcctct ctgttggggcctggggctgc agaacacacc 1680 tgcgtttcac tggccttcat taggtggccc tagggagatggctttctgct ttggatcact 1740 gttccctagc atgggtcttg ggtctattgg catgtccatggccttcccaa tcaagtctct 1800 tcaggccctc agtgaagttt ggctaaaggt tggtgtaaaaatcaagagaa gcctggaaga 1860 catcatggat gccatggatt agctgtgcaa ctgaccagctccaggtttga tcaaaccaaa 1920 agcaacattt gtcatgtggt ctgaccatgt ggagatgtttctggacttgc tagagcctgc 1980 ttagctgcat gttttgtagt tacgattttt ggaatcccactttgagtgct gaaagtgtaa 2040 ggaagctttc ttcttacacc ttgggcttgg atattgcccagagaagaaat ttggcttttt 2100 ttttcttaat ggacaagaga cagttgctgt tctcatgttccaagtctgag agcaacagac 2160 cctcatcatc tgtgcctgga agagttcact gtcattgagcagcacagcct gagtgctggc 2220 ctctgtcaac ccttattcca ctgccttatt tgacaaggggttacatgctg ctcaccttac 2280 tgccctggga ttaaatcagt tacaggccag agtctccttggagggcctgg aactctgagt 2340 cctcctatga acctctgtag cctaaatgaa attcttaaaatcaccgatgg aaccaaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2432 512340 DNA Homo sapiens misc_feature (96) n equals a,t,g, or c 51gacgctgggg gcgggtgggg gcgcggggta ccgggctgga cggccggccg gcgccccctc 60attagtatgc ggacgaagcg gcgggctgcg cggagngacg tcccctgcag ccgcggaccg 120aggcagcggc ggcacctgcc ggccgagcaa tgccaagtga gtacacctat gtraaactga 180gaagtgattg ctcgaggcct tccctgcaat ggtacacccg agctcaaagc aagatgagaa 240ggcccagctt gttattaaaa gacatcctca aatgtacatt gcttgtgttt ggagtgtgga 300tcctttatat cctcaagtta aattatacta ctgaagaatg tgacatgaaa aaaatgcatt 360atgtggaccc tgaccatgta aagagagctc agaaatatgc tcagcaagtc ttgcagaagg 420aatgtcgtcc caagtttgcc aagacatcaa tggcgctgtt atttgagcac aggtatagcg 480tggacttact cccttttgtg cagaaggscc ccaaagacag tgaagctgag tccaagtacg 540atcctccttt tgggttccgg aagttctcca gtaaagtcca gaccctcttg gaactcttgc 600cagagcacga cctccctgaa cacttgaaag ccaagacctg tcggcgctgt gtggttattg 660gaagcggagg aatactgcac ggattagaac tgggccacac cctgaaccag ttcgatgttg 720tgataaggtt aaacagtgca ccagttgagg gatattcaga acatgttgga aataaaacta 780ctataaggat gacttatcca gagggcgcac cactgtctga ccttgaatat tattccaatg 840acttatttgt tgctgtttta tttaagagtg ttgatttcaa ctggcttcaa gcaatggtaa 900aaaaggaaac cctgccattc tgggtacgac tcttcttttg gaagcaggtg gcagaaaaaa 960tcccactgca gccaaaacat ttcaggattt tgaatccagt tatcatcaaa gagactgcct 1020ttgracatcc ttcagtactc agagcctcag tcaaggttct gggggccgag ataagaacgt 1080ccccacaatc ggtgtcattg ccgttgtctt agccacacat ctgtgcgatg aagtcagttt 1140ggcgggtttt ggatatgacc tcaatcaacc cagaacacct ttgcactact tcgacagtca 1200atgcatggct gctatgaact ttcagaccat gcataatgtg acaacggaaa ccaagttcct 1260cttaaagctg gtcaaagagg gagtggtgaa agatctcagt ggaggcattg atcgtgaatt 1320ttgaacacag aaaacctcag ttgaaaatgc aactctaact ctgagagctg tttttgacag 1380ccttcttgat gtatttctcc atcctgcaga tactttgaag tgcagctcat gtttttaact 1440tttaatttaa aaacacaaaa aaaattttag ctcttcccac tttttttttc ctatttattt 1500gaggtcagtg tttgtttttg cacaccattt tgtaaatgaa acttaagaat tgaattggaa 1560agacttctca aagagaattg tatgtaacga tgttgtwttg atttttaaga aagtaattta 1620atttgtaaaa cttctgctcg tttacactgc acattgaata caggtaacta attggaagga 1680gaggggaggt cactcttttg atggtggccc tgaacctcat tctggttccc tgctgcgctg 1740cttggtgtga cccacggagg atccactccc aggatgacgt gctccgtagc tctgctgctg 1800atactgggtc tgcgatgcag cggcgtgagg cctgggctgg ttggagaagg tcacaaccct 1860tctctgttgg tctgccttct gctgaaagac tcgagaacca accagggaag ctgtcctgga 1920ggtccctggt cggagaggga catagaatct gtgacctctg acaactgtga agccaccctg 1980ggctacagaa accacagtct tcccagcaat tattacaatt cttgaattcc ttggggattt 2040tttactgccc tttcaaagca cttaagtgtt agatctaacg tgttccagtg tctgtctgag 2100gtgacttaaa aaatcagaac aaaacttcta ttatccagag tcatgggaga gtacaccctt 2160tccaggaata atgttttggg aaacactgaa atgaaatctt cccagtatta taaattgtgt 2220atttaaaaaa aagaaacttt tctgaatgcc tactggcggt gtataccagg cagtgtgcca 2280gtttaaaaag atgaaaaaga ataaaaactt ttgaggaama aaaaaaaaaa aaaaactcga 234052 601 DNA Homo sapiens misc_feature (115) n equals a,t,g, or c 52agtaggggag actgagactg accggtagcc aggcaggcgg acgacgcacg cccggacaga 60ctgagcaggc gccggagaac cactcacagg ttccccccgc ctttcccttt gaaanctagg 120cttttgcctt tcccgtggcg cccgagagag aatgctggac tctgccgact tcagcgcaac 180taangatttc tcaagctagg ggacaaacga tcagcccaat cctgagaagg ggggaaccaa 240gcaccccgtc cccatccccc tcccctcccc cgactaaact cgggcgccaa acccagccct 300tctctaacca ccctacttcc tcctctcctt tctagcatgg tggctgtatg gacagtctga 360cagaacagag actgacatct cccaatctgc cggcccccca cctggaacac tacagtgttc 420tgcattgcac catgaccctg gatgtgcaaa ctgtagtcgt ttttgccgtg attgtagtcc 480tcctgcttgt caatgtcata ctcatgtttt tcctgggaac gcgctgaatg gagtccagnc 540acctgagctg tcgcgaactc tcgctttgat ttcatcccga gagccaccga gaagaaaaaa 600 a601 53 359 DNA Homo sapiens misc_feature (343) n equals a,t,g, or c 53ctcgtgccga attcggcacg agagatggta cttttaagag gtaattaggt tgctaagatg 60gattaacatc tttctcttga cactgagact gggttctcct gggaatggtt agttcccaag 120agagtgagtt gttataaaac aatgctgcct cttctatttt gcgctttttg tttgcacaaa 180ctcggtcccc ttctgtttct ctacgatgtt ttgatgcrgc atgaggcagt catgagaacc 240caccagatac agctgcctga tcctgaattt cccagccaac agaaccaagt gctaaataaa 300actcttttta ataagttaaa aaaaaaaaaa aaaaaaaaaa aanaaanana aaaaaaaaa 359 541141 DNA Homo sapiens 54 ggcacgagct gctgaggcgt gagaatggcg tcccgcggccggcgtccgga gcatggcgga 60 cccccagagc tgttttatga cgagacagaa gcccggaaatacgttcgcaa ctcacggatg 120 attgatatcc agaccaggat ggctgggcga gcattggagcttctttatct gccagagaat 180 aagccctgtt acctgctgga tattggctgt ggcactgggctgagtggaag ttatctgtca 240 gatgaagggc actattgggt gggcctggat atcagccctgccatgctgga tgaggctgtg 300 gaccgagaga tagagggaga cctgctgctg ggggatatgggccagggcat cccattcaag 360 ccaggcacat ttgatggttg catcagcatt tctgctgtgcagtggctctg taatgctaac 420 aagaagtctg aaaaccctgc caagcgcctg tactgcttttttgcttctct tttttctgtt 480 ctcgtccggg gatcccgagc tgtcctgcag ctgtaccctgagaactcaga gcagttggag 540 ctgatcacaa cccaggccac aaaggcaggc ttctccggtggcatggtggt agactaccct 600 aacagtgcca aagcaaagaa attctacctc tgcttgttttctgggccttc gacctttata 660 ccagaggggc tgagtgaaaa tcaggatgaa gttgaacccagggagtctgt gttcaccaat 720 gagaggttcc cattaaggat gtcgaggcgg ggaatggtgaggaagagtcg ggcatgggtg 780 ctggagaaga aggagcggca caggcgccag ggcagggaagtcagacctga cacccagtac 840 accggccgca agcgcaagcc ccgcttctaa gtcaccacgcggttctggaa aggcacttgc 900 ctctgcactt ttctatattg ttcagctgac aaagtagtattttagaaaag ttctaaagtt 960 ataaaaatgt tttctgcagt aaaaaaaaag ttctctgggccgggcgtggt ggctcacacc 1020 tgtaatccca gcaccttggg aggctgaggt gggaggatcatttgaggcca ggagtttgag 1080 acctgcctgg gcaacataat gaaacttcct ttccagggagaaaaaaaaaa aaaaaaaaaa 1140 a 1141 55 1560 DNA Homo sapiens misc_feature(8) n equals a,t,g, or c 55 gagagagnga gagaggtatc actgcaaggc tactatgagtattttcaaat caccacatct 60 tatcctgagc aagaggtcac tgttctgtgc tatggtaagatacaaactat tccttcatat 120 ataataaaat tccacctttt ttcaaaatta atatagggtaagtgaagtct mccaatcatg 180 acrgcaragg aaattagtgt ctaaatgrac tgtgrgttacaggtaccttt cactwagggg 240 caggcaggtt tttataaaaa accmtgtggt aatcatcmattgccattaag ctcctattac 300 tagcttttaa gaccatttta taaagattat ctggtgcctaattaacaaga aagaaattag 360 actcaggttt aagatgctgc tggtgttctg aaattactctgaaaggtcat tcaaagaact 420 tcaaacttaa aatttttcat tcatgtattt attccacagtcaaaataaat caaaatttaa 480 agctataaca tttttaaaag ataaaggaga atttgtggcacagctgcatt aacaaaacag 540 acaccagtct aaagtgcaac actaaacagg tattctctgttcccacggtg gaataaatac 600 acacaattac acataagatt tcactaaaga taggagatgaggcaaataac cctttgaaat 660 tacctgccca acaaatagag gcaggctaca ttaatttaacattttactgc aaaatggaaa 720 aaatccccga ggtgactaac tcaaactcct catttcatgcacatgacctt ggcttctgtg 780 ttctttccat agccacatcc aaatccagaa aggctcctgcaccccatgct caaaaatgca 840 acctcaagtc cctgaggtcc tcagcacaga ctgacattaacaagcctgtg ttcagccttc 900 atccagaacc tccagggaaa tcaggagcac aaacacagagcaaagcaccg tttctttaaa 960 caatggcttt aactgtcgaa tgagctctga caagccatatgcatttcata aacaaaccaa 1020 aacatcatct tcatatcttc ctatttttct tgcaaaaatgttaagccatc caagtaaaaa 1080 aaaaaatttt aatttaacaa tgaaaaagga acttcaaagggtttatgcca aaaaacaaac 1140 cagtcctctg cagcctaact catttgtttt tgggctgcgaagccatgtag agggcgatca 1200 ggcagtagat ggtccctccc acagtcagcg ccatggtggtccggtaaagc atttggtcag 1260 gcaggcctcg tttcaggtag acgggcacac catcagctttctggaaaaac ttttgtagct 1320 ctggaacttt gtttttccca gcataatcat acactgtggaatcggaggtc agtttagttg 1380 gtgtggcaaa tatgataggt ggtgcttctg tggaaaccacaggctttnaa tctgcgggct 1440 ataggcctcc gaagcccatg ctcctgccaa cttctgcgtgaagccactaa acttgtagta 1500 catgacgccc agagtccggc ttcccgcatc cgctgccaacgcgaccgccc cagagaagga 1560 56 1507 DNA Homo sapiens misc_feature (1047)n equals a,t,g, or c 56 ggaacgcaga gcggagcgtg gagagcggag cgaagctggataacagggga ccgatgatgt 60 ggcgaccatc agttctgctg cttctgttgc tactgaggcacggggcccag gggaagccat 120 ccccagacgc aggccctcat ggccagggga gggtgcaccaggcggccccc ctgagcgacg 180 ctccccatga tgacgcccac gggaacttcc agtacgaccatgaggctttc ctgggacggg 240 aagtggccaa ggaattcgac caactcaccc cagaggaaagccaggcccgt ctggggcgga 300 tcgtggaccg catggaccgc gcgggggacg gcgacggctgggtgtcgctg gccgagcttc 360 gcgcgtggat cgcgcacacg cagcagcggc acatacgggactcggtgagc gcggcctggg 420 acacgtacga cacggaccgc gacgggcgtg tgggttgggaggagctgcgc aacgccacct 480 atggccacta cgcgcccggt gaagaatttc atgacgtggaggatgcagag acctacaaaa 540 agatgctggc tcgggacgag cggcgtttcc gggtggccgaccaggatggg gactcgatgg 600 ccactcgaga ggagctgaca gccttcctgc accccgaggagttccctcac atgcgggaca 660 tcgtgattgc tgaaaccctg gaggacctgg acagaaacaaagatggctat gtccaggtgg 720 aggagtacat cgcggatctg tactcagccg agcctggggaggaggagccg gcgtgggtgc 780 agacggagag gcagcagttc cgggacttcc gggatctgaacaaggatggg cacctggatg 840 ggagtgaggt gggccactgg gtgctgcccc ctgcccaggaccagcccctg gtggaagcca 900 accacctgct gcacgaragc gacacggaca aggaygggcggctgagcaaa gcgsaaatcc 960 tgggtaattg gaacatgttt gtgggcagtc aggccaccaactatggygag gacctgaccc 1020 ggcaccacga tgagctgtga gcmccgngca cctgccacagcctcagaggc ccgcacaatg 1080 accggaggag gggccgctgt ggtctggccc cctccctgtccaggccccgc aggaggcaga 1140 tgcagtccca ggcatcctcc tkcccctggg ctctcagggaccccctgggt cggcttctgt 1200 ccctgtcaca cccccaaccc cagggagggg ctgtcatagtcccagaggat aagcaatacc 1260 tatttctgac tgagtctccc agcccagacc cagggaccctnggccccaag ctcagctcta 1320 agaaccgccc caacccctcc agctccaaat ctgagcctccaccacataga ctgaaactcc 1380 cctggcccca gccctctcct gcctggcctg gcctgggacacctcctctct gccaggaggc 1440 aataaaagcc agcgccggga aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa 1500 aaaaaan 1507 57 450 DNA Homo sapiens 57tttttttact cgaaaaaatg tttaatagaa tttaaaattt taacttcagg gaatttggaa 60gttcaatcat tctcaaagag gctgtaagga tgattaaaat cctgaaggaa gccattgaag 120aaacttcctt ctgctctttc tggaggatct cttttcaatt atctattcat catatatttc 180ttatcttctg tgcacaattg acaactcttc tttacagcac attcctctty attcccatct 240cttggtttct gattgttcct ggggctgtgg ataaaaccat tctctgagaa gctgataagc 300aattggatga gaaagargga gargaaaact ggcaggarga tctggsccca tgcccgcagc 360cagcacatct ctcttcagac ctggtgaccc cagccactgg gaacctggca ggcaccagct 420acagtgttgg acactgctcg tgccgaattc 450 58 1147 DNA Homo sapiens 58ggcacgagac ccattgagca gaaggaggcc aggtgggaaa gctcctggga agagcagcca 60gactggacac tgggctgctt gagtcctgag tcacaattca gaattcctgg gctccctggg 120tgcattctat cattccagtt gaaagtttgc ttccttccag tcatgtggct cttcattcta 180ctctccttgg ctctcatttc agatgccatg gtcatggatg aaaaggtcaa gagaagcttt 240gtgctggaca cggcttctgc catctgcaac tacaatgccc actacaagaa tcaccccaaa 300tactggtgcc gaggctattt ccgtgactac tgcaacatca tcgccttctc ccctaacagc 360accaatcatg tggccctgaa ggacacaggg aaccagctca ttgtcactat gtcctgcctg 420aacaaagaag acacgggctg gtactggtgt ggcatccagc gggactttgc cagggatgac 480atggatttta cagagctgat tgtaactgac gacaaaggaa cctggccaat gactttggtc 540tgggaaagac tatcaggcac aaaaccagaa gctgcaaggc tcccaaagtt gtccgcaagg 600ctgaccgctc caggacgtcc attctcatca tttgcatact gatcacgggt ttgggaatca 660tctctgtaat cagtcatttg accaaaagga ggagaagtca aaggaataga agggtaggca 720acactttgaa gcccttctcg cgtgtcctga ctccaaagga aatggctcct actgaacaga 780tgtgactgaa gattttttta atttagttca taaagtgatg ctacaacaga ataatcacca 840tgacaactgg ccccacacct cagagactga ttctgatctc ccaggaattc tgaaggtccc 900tctatccttg acaacaatca tttgcagcca ggtagcaacg gcagtagtca gaggagctat 960gatagaccac acccaagcaa ggctgccctc aaataacatc tcaagatctt agttcttatg 1020cattccatca gtcagaagtg aagaagaggt ggagaatctg gattggggac caggaaatca 1080cttgtatttt gttagccaat aaattcctag ccagtgttga atgaaaaaaa aaaaaaaaaa 1140aaaaaaa 1147 59 777 DNA Homo sapiens 59 ggcagaggct cctcagaagg gcgtgggctctccagtcttc cacagtcccc accatgccct 60 gttgccttac cgctgacgta gctcacccatcttttacttg cctggctaag atgcatggca 120 tywcatttcc tccttgttgc actgcagtcagtccctcact gcccccatct cctggaagag 180 gagcataagc tttgcaaggt cagccacttctctggggtca cactagttac atcaagacag 240 gactccagct catatgtgcc agtgcagacactcttcatcc acctggggcc ctgggcttgg 300 gacctggytc cttgcacagc agargacccggaggctgaga ggagcttgcg gttgtgtcat 360 agtcacctgg ccagarggaa cgtgagcccctcccaagctg cagarggarg garcargcgt 420 ggctgtcagc accgaggtag cagagaattaacattcttgt cagcagagaa tgaagcagga 480 atataattaa aactttgccc ttggaatagctgattcattt gaattttatt ccacacgttt 540 gaaagaggaa agaaaatgtg aagacttgcagcctggttct cgcctggcct gggctggccc 600 agctgtcagg cccggttcct ttctgagcattcagtccact gatgttgact gagggccagg 660 agagaccctc agcagggtat taccatatcagcctcctatc gctgctggga gaaattacca 720 tgaattcagt ggcttaaaac aacacacgagcctctctgag cctaccctgg ctcagga 777 60 1191 DNA Homo sapiens misc_feature(5) n equals a,t,g, or c 60 aagantgatt ttccttactc tccaaagcgt cagcattttgaagtttcttt tatgaaagtg 60 ggggcaagaa tcagggtgaa aatgagtgta aacaaagcccatcctgtggt cagcacccac 120 tggaggtggc cagcagagtg gcctcagatg ttcctgcacctggcccagga gcccaggaca 180 gaggtcaaat ctaggcccct tggtctggct ggattcatcaggcaagattc gaaaacaaga 240 aaacctctag aacaagaaac aatcatgtct gcagcagatacggcactgtg gccctatggc 300 catggcaatc gtgagcacca agagaatgag ttacagaaatatctccaata caaagacatg 360 catctcctgg acagtggaca gtcgctggga cacacacacacacttcaagg ctcacacaac 420 ctaacagcct taaatatctg aagaaacaga atcacgacattaagtcagca gagggagagg 480 taggctgaag cagcaggagg ccaattttat atcccacagatttttttaaa aatgactccc 540 cagcaagggg tggggagaaa gccactgatt taggagagttcttggctcag ccaaccactg 600 cggttatcta cacgttttac aaaggcacrg aagtagagaggggctgcact cacgaccctc 660 cccagggccc gcacagccag acacggtggg ttcttcctttttcccttctg gccttggtgg 720 aattcctacc acggtggcct ctgcctttgg gacaatgccttcatgctcat ccccgggtca 780 aggatggagt ctgttaccat tttccagggg aaattccaaggaccagcccc gcctcattac 840 gttcacccca caggaaggtg atctggaaag cctgtaaacacgtactctgg gtggctgagt 900 ggtgtcacca agctgctttt gtgcagggct gaagcacagacaagagggca ggcagctgcc 960 ggaggcctga agtggggaga gatccccgca ggcctgcaggagccagggag aacctccaac 1020 tggatctaaa ctgtgggaca gcccaggcgt gcccctcttcacatggctcc caggctccct 1080 caaagccctt cccaggccct gcaggaagag agggagggtgaggagaggca gggagggcag 1140 aggtcgcctg aaagcctggg ctccgaactc cctcagcagagctttaaagt g 1191 61 1580 DNA Homo sapiens misc_feature (1567) n equalsa,t,g, or c 61 ccccgccccc cgcccacgaa ggaagtggct gctgctccgg cgcggacccagagccggttc 60 ggcgcgtcga ctgcccagag tccgcggccg ggcgcgggag gagccaagccgccatggcct 120 accacagctt cctggtggag cccatcagct gccacgcctg gaacaaggaccgcacccaga 180 ttgccatctg ccccaacaac catgaggtgc atatctatga aaagagcggtgccaaatgga 240 ccaaggtgca cgagctcaag gagcacaacg ggcaggtgac aggcatcgactgggcccccg 300 agagtaaccg tattgtgacc tgcggcacag accgcaacgc ctacgtgtggacgctgaagg 360 gccgcacatg gaagcccacg ctggtcatcc tgcggatcaa ccgggctgcccgctgcgtgc 420 gctgggcccc caacgagaac aagtttgctg tgggcagcgg ctctcgtgtgatctccatct 480 gttatttcga gcaggagaat gactggtggg tttgcaagca catcaagaagcccatccgct 540 ccaccgtcct cagcctggac tggcacccca acaatgtgct gctggctgccggctcctgtg 600 acttcaagtg tcggatcttt tcagcctaca tcaaggaggt ggaggaacggccggcaccca 660 ccccgtgggg ctccaagatg ccctttgggg aactgatgtt cgaatccagcagtagctgcg 720 gctgggtaca tggcgtctgt ttctcagcca gcgggagccg cgtggcctgggtaagccacg 780 acagcaccgt ctgcctggct gatgccgaca agaagatggc cgtcgcgactctggcctctg 840 aaacactacc actgctggcg ctgaccttca tcacagacaa cagcctggtggcagcgggcc 900 acgactgctt cccggtgctg ttcacctatg acgccgccgc ggggatgctgagcttcggcg 960 ggcggctgga cgttcctaag cagagctcgc agcgtggctt gacggcccgcgagcgcttcc 1020 agaacctgga caagaaggcg agctccgagg gtggcacggc tgcgggcgcgggcctagact 1080 cgctgcacaa gaacagcgtc agccagatct cggtgctcag cggcggcaaggccaagtgct 1140 cgcagttctg caccactggc atggatggcg gcatgagtat ctgggatgtgaagagcttgg 1200 agtcagcctt gaaggacctc aagatcaaat gacctgtgag gaatatgttgccttcatcct 1260 agctgctggg gaagcgggga gaggggtcag ggaggctaat ggttgctttgctgaatgttt 1320 ctggggtacc aatacgagtt cccatagggg ctgctccctc aaaaagggaggggacagatg 1380 gggagctttt cttacctatt caaggaatac gtgccttttt cttaaatgctttcatttatt 1440 gaaaaaaaaa aaaaatgccc ccaaagcact atgctggtca tgaactgcttcaaaatgtgg 1500 aggtaataaa atgcaactgt gtaaaaaaaa aaaaaaaaaa aaatgaccctcgcgatctag 1560 aactagncgg acgcntgggt 1580 62 1117 DNA Homo sapiens 62ggcacgaggc gcgatgcagc acaggctaga ggctgcgcaa sgcgggggcc cgcccctggg 60accctccggg ccgggcggtt tggcccctta gcgcccgggc gtcggggcgg taaaaggccg 120gcagaaggga ggcacttgag aaatgtcttt cctccaggac ccaagtttct tcaccatggg 180gatgtggtcc attggtgcag gagccctggg ggctgctgcc ttggcattgc tgcttgccaa 240cacagacgtg tttctgtcca agccccagaa agcggccctg gagtacctgg aggatataga 300cctgaaaaca ctggagaagg aaccaaggac tttcaaagca aaggagctat gggaaaaaaa 360tggagctgtg attatggccg tgcggaggcc aggctgtttc ctctgtcgag aggaagctgc 420ggatctgtcc tccctgaaaa gcatgttgga ccagctgggc gtccccctct atgcagtggt 480aaaggagcac atcaggactg aagtgaagga tttccagcct tatttcaaag gagaaatctt 540cctggatgaa aagaaaaagt tctatggtcc acaaaggcgg aagatgatgt ttatgggatt 600tatccgtctg ggagtgtggt acaacttctt ccgagcctgg aacggaggct tctctggaaa 660cctggaagga gaaggcttca tccttggggg agttttcgtg gtgggatcag gaaagcaggg 720cattcttctt gagcaccgag aaaaagaatt tggagacaaa gtaaacctac tttctgttct 780ggaagctgct aagatgatca aaccacagac tttggcctca gagaaaaaat gattgtgtga 840aactgcccag ctcagggata accagggaca ttcacctgtg ttcatgggat gtattgtttc 900cactcgtgtc cctaaggagt gagaaaccca tttatactct actctcagta tggattatta 960atgtatttta atattctgtt taggcccact aaggcaaaat agccccaaaa caagactgac 1020aaaaatctga aaaactaatg aggattatta agctaaaacc tgggaaatag gaggcttwaa 1080atgactgccm gctggtgcrt gctcacactt ggcccac 1117 63 361 DNA Homo sapiens 63cccacgcgtg ckggcgcctg gcagccaccg cctgggaggt tactgtaagg cccgcagctc 60ccgccagctc ccgcggacts ctgccgcctc cttaccatga agccagtaag tcgtcgcacg 120ctggactgga tttattcagt gttgctgctt gccatcgttt taatctcctg gggctgcatc 180atctatgctt cgatggtgtc tgcaagacga cagctaagga agaaataccc agacaaaatc 240tttgggacga atgaaaattt gtaactcttc tggatttaat tatctgaaaa tacagttctt 300tccctcatgc ttatgtagat ataaaaataa aattcataat gcaaaaaaaa aaaaaaaaaa 360 g361 64 1668 DNA Homo sapiens misc_feature (1664) n equals a,t,g, or c 64ggcacgaggt ctgccaagct atagaccatg gctgtgaaca catttgtgtg aacagtgacg 60actcatacac gtgcgagtgc ttggagggat tccggctcgc tgaggatggg aaacgctgcc 120gaagaaggat gtctgcaaat caacccacca tggctgcgaa cacatttgtg ttaataatgg 180gaattcctac atctgcaaat gctcakaggg atttgttcta gctgaggacg gaagacggtg 240caagaaatgc actgaaggcc caattgacct ggtctttgtg atcgatggat ccaagagtct 300tggagaagag aattttgagg tcgtgaagca gtttgtcact ggaattatag attccttgac 360aatttccccc aaagccgctc gagtggggct gctccagtat tccacacagg tccacacaga 420gttcactctg agaaacttca actcagccaa agacatgaaa aaagccgtgg cccacatgaa 480atacatggga aagggctcta tgactgggct ggccctgaaa cacatgtttg agagaagttt 540tacccaagga gaaggggcca ggccctttcc acaagggtgc ccagagcagc cattgtgttc 600accgacggac gggctcagga tgacgtctcc gagtgggcca gtaaagccaa ggccaatggt 660atcactatgt atgctgttgg ggtaggaaaa gccattgagg aggaactaca agagattgcc 720tctgagccca caaacaagca tctcttctat gccgaagact tcagcacaat ggatgagata 780agtgaaaaac tcaagaaagg catctgtgaa gctctagaag actccgatgg aagacaggac 840tctccagcag gggaactgcc aaaaacggtc caacagccaa cagtgcaaca cagatatctg 900tttgaagaag acaatctttt acggtctaca caaaagcttt cccattcaac aaaaccttca 960ggaagccctt tggaagaaaa acacgatcaa tgcaaatgtg aaaaccttat aatgttccag 1020aaccttgcaa acgaagaagt aagaaaatta acacagcgct tagaagaaat gacacagaga 1080atggaagccc tggaaaatcg cctgagatac agatgaagat tagaaatcgc gacacatttg 1140tagtcattgt atcacggatt acaatgaacg cagtgcagag ccccaaagct caggctattg 1200ttaaatcaat aatgttgtga agtaaaacaa tcagtactga gaaacctggt ttgccacaga 1260acaaagacaa gaagtataca ctaacttgta taaatttatc taggaaaaaa atccttcaga 1320attctaagat gaatttacca ggtgagaatg aataagctat gcaaggtatt ttgtaatata 1380ctgtggacac aacttgcttc tgcctcatcc tgccttagtg tgcaatctca tttgactata 1440cgataaagtt tgcacagtct tacttctgta gaacactggc cataggaaat gctgtttttt 1500tgtaytggac tttaccttga tatatgtata tggatgtatg cataaaatca taggacatat 1560gtacttgtgg aacaagttgg attttttata caatattaaa attcaccact tcagagraaa 1620aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaanaaaa 1668 65 1353 DNAHomo sapiens misc_feature (1322) n equals a,t,g, or c 65 gggtcgacccacgcgtccgc ccacgcgtcc ggatggctgc gctgttgctg agacacgttg 60 gtcgtcattgcctccgagcc cactttagcc ctcagctctg tatcagaaat gctgttcctt 120 tgggaaccacggccaaagaa gagatggagc ggttctggaa taagaatata ggttcaaacc 180 gtcctctgtctccccacatt actatctaca gttggtctct tcccatggcg atgtccatct 240 gccaccgtggcactggtatt gctttgagtg caggggtctc tctttttggc atgtcggccc 300 tgttactccctgggaacttt gagtcttatt tggaacttgt gaagtccctg tgtctggggc 360 cagcactgatccacacagct aagtttgcac ttgtcttccc tctcatgtat catacctgga 420 atgggatccgacacttgatg tgggacctag gaaaaggcct gaagattccc cagctatacc 480 agtctggagtggttgtcctg gttcttactg tgttgtcctc tatggggctg gcagccatgt 540 gaagaaaggaggctcccagc atcatcttcc tacacattat tacattcacc catctttctg 600 tttgtcattcttatctccag cctgggaaaa gttctcctta tttgtttaga tccttttgta 660 ttttcagatctccttggagc agtagagtac ctggtagacc ataatagtgg aaaagggtct 720 agttttccccttgtttctaa agatgaggtg gctgcaaaaa ctcccctttt ttgcccacag 780 cttgcctactctcggcctag aagcagttat tctctctcca tattgggctt tgatttgtgc 840 tgagggtcagcttttggctc cttcttcctg agacagtgga aacaatgcca gctctgtggc 900 ttctgccctggggatgggcc gggttggggg gtgggttggt gaggctttgg gtgccactgc 960 ctgtgggttgctggcttaaa ggacaattct cttcattggt gagagcccag gccattaaca 1020 cctacacagtgttattgaaa gaagagaggt gggggtggag gggaattagt ctgtcccagc 1080 tagagggagataaagagggc tagttagttc ttggagcagc tgcttttgag gagaaaatat 1140 atagctttggacacgaggaa gatctagaaa attatcattg aacatattaa tggttatttc 1200 tttttcttggatttccagaa aagcctctta attttatgct ttctcatcga agtaatgtac 1260 cctttttttctgaaactgaa ttaaatactc attttatctt tgaaaaaaaa aaaaaaaacc 1320 tnggggggggccccggaccc naattggccc tat 1353 66 1011 DNA Homo sapiens misc_feature(951) n equals a,t,g, or c 66 cggaagaaag cagccatcca gacatttcagaacacgtacc aggtgttagc tgtgaccttc 60 aatgacacaa gtgatcagat tatttctggtggaatagaca atgatatcaa ggtctgggac 120 tgcgccagaa caagctaacc tacaccatgagaggccatgc agattcagtg actggcctga 180 gtttaagttc tgaaggctct tatcttttgtccaatgcaat ggacaataca gttcgtgtct 240 gggatgtccg gccatttgcc cccaaagagagatgtgtaaa gatatttcaa ggaaatgtgc 300 acaactttga aaagaacctt ctgagatgttcttggtcacc tgatggaagc aaaatagcag 360 ctggctcagc cgacaggttt gtttatgtgtgggataccac aagcaggaga atattgtata 420 agctgcccgg ccatgctggc tccatcaatgaagtggcttt ccaccctgat gagcccatca 480 ttatctcagc atcgagtgac aagagactgtatatgggaga gattcagtga agatatggac 540 tggaagactc caaggccgct tgtctttgagacctcagact gcataagtga tgccaaatgt 600 tggatgtcca ggytagcacc ctcccttcagatgaccattg ctagcaagaa acaggaggcg 660 gtggccatat tccaaaaacc acttctgtcccatttcacca ggatgactaa ggcaagctcc 720 ctgtggcctc taaaaaccac ctgccagatttcagggactg tttttttttt tctttttctt 780 ttttcctgtt ttctaatgca ggcccaatgtgacaaatttg ttggttggga tttttttttt 840 tttttgtaac tggcttgtat gatattttctttctgtattt ctctatatca ttttgtatta 900 aaagccaaat agatgccttt ttacaagarmaaaaaaaaaa aaaaaaaaaa nnaaaaaaaa 960 ctgggagggg gggcccggta cccaaatcgccggatatgat cgtaaacaat c 1011 67 1193 DNA Homo sapiens misc_feature (512)n equals a,t,g, or c 67 ggccgggcgg tgcgcactgc gggcgcatcc ctgccccggcgccgtccgtg cccgcgggac 60 ctgacagccg ggtcagaggg cgaactgtgc tcaggcccgggctggacgca gagccagagc 120 tgtccccaga ggagcagagg gtcctggaaa ggaagctgaaaaaggaacgg aagaaagagg 180 agaggcagcg tctgcgggag gcaggccttg tggcccagcacccgcctgcc aggcgctcgg 240 gggccgaact ggcctgggac tacctctgca gatgggcccaaaagcacaag aactggaggt 300 ttcagaagac gaggcagacg tggctcctgc tgcacatgtatgacagtgac aaggttcccg 360 atgagcactt ctccaccctg ctggcctacc tggaggggctgcagggccgg gcccgagagc 420 tgacggtgca gaaggcggaa gcctgatgcg ggagctggatgaggagggct ctgatccccc 480 cctgccgggg agggcccagc gcatccgaca gntgctgcagctgctctcct agtgggttca 540 gcgcggggcg gggccgctgc ccagtgcagg gctgcctcagaccacacagg gtgcagctcc 600 tccggcggtg ggggccgggt tcaccagcag ggcagcggctgagcaagggc tttcagctcc 660 tccggtggtg ggggccggga tcaccagcac cagagcctcgcaagggcccc ttccctcctc 720 cagaccctcc ttggccggtg acgctgtgac agtgatggcaggttcagtgc cttcagcgca 780 gagcgtggat gctctggaat cacccggacc cctggccttggagggaccct ccagccccag 840 gaatctgctt tggagggaaa tgtctatttt tctaccgggaatattttaga gattggggca 900 tgctggctcc tcccgccagc tgcaaacctg caccttccgcctgattcccg atccccctgc 960 gtgggccgca ttcctggtcc cctgcctgcg tccatcgaggggcctggctg tggcctgttt 1020 tcctttgacc ccacacagcg tcattgcggg tcatggggagcccctggtgg gagcttgtgg 1080 agtcggatca cgtacctgtg cagaaaccgc ctctgtggctgcatttgaaa taaaacccga 1140 cccagcagca aaaaaaaaaa aaaaaancnc nagggggggcccggnaccca att 1193 68 560 DNA Homo sapiens 68 gaattcggca cgagttggcacatgatgcaa aatgcatttc tcagagtaga ttgcagtcaa 60 aaatgttgga aactactaagcatgtgcara tagcatgcat gctgctgctg acctgccaga 120 tatttctccc ttcctccctttctccctcat ttattcattc attaactgat tcattcatcc 180 cattaaaaaa attatatgtatgttttgtgc aaagcaccct actcaaggct gcggggtaca 240 aaagtatatc agaagccttgggctttgacm wacttctctg tagtagtgct agatttgtgt 300 ggatctgcca cacttactccaggcctcttg tgacctgtgc tttgcattaa tctcttaggc 360 taagccacat accttttcattatacaatct ttgctgatgc taaggacaga ttccaaagtg 420 ccctccttat aatttttgtatttaatgcaa agtgtaatca agaataggcc attgttaggt 480 caattgcttt tctgtatttatcttttcaaa caataaataa tcagtgggat gaaaaagggc 540 cggaaaaaaa aaaaaaaaaa560 69 1657 DNA Homo sapiens misc_feature (6) n equals a,t,g, or c 69cggacngagc cgccgccggg cacttcctgt ggaggccgca gcgggtgcgg gcgccgacgg 60gcgagagcca gcgagcgagc gagcgagccg agccgagcct cccgccgtcg ccatgggcca 120gaacgacctg atgggcacgg ccgaggactt cgccgaccag ttcctccgtg tcacaaagca 180gtacctgccc cacgtggcgc gcctctgtct gatcagcacc ttcctggagg acggcatccg 240tatgtggttc cagtggagcg agcagcgcga ctacatcgac accacctgga actgcggcta 300cctgctggcc tcgtccttcg tcttcctcaa cttgctggga cantgactgg ctgcgtcctg 360gtgttgagca ggaacttcgt gcagtacgcc tgcttcgggc tctttggaat catagctctg 420cagacgattg cctacagcat tttatgggac ttgaagtttt tgatgaggaa cctggccctg 480ggaggaggcc tgttgctgct cctagcagaa tcccgttctg aagggaagag catgtttgcg 540ggcgtcccca ccatgcgtga gagctccccc aaacagtaca tgcagctcgg aggcagggtc 600ttgctggttc tgatgttcat gaccctcctt cactttgacg ccagcttctt ttctattgtc 660cagaacatcg tggggcacag ctctgatgat tttagtggcc attggtttta aaaccaagct 720ggctgctttg actcttgttg tgtggctctt tgccatcaac gtatatttca acgccttctg 780gaccattcca gtctacaagc ccatgcatga cttcctgaaa tacgacttct tccagaccat 840gtcggtgatt gggggcttgc tcctggtggt ggccctgggc cctgggggtg tctccatgga 900tgagaagaag aaggagtggt aacagtcaca gatccctacc tgcctggcta agacccgtgg 960ccgtcaagga ctggttcggg gtggattcaa caaaactgcc agcttttatg tatcctcttc 1020ccttcccctc ccttggtaaa ggcacagatg ttttgagaac tttatttgca gagacacctg 1080agaatcaatg gcttcaggac atgggttctc ttctcctgtg atcattcaag tgctcactgc 1140atgaagactg gcttgtctca gtgtttcaac ctcaccaggg ctgtctcttg gtccacacct 1200cgctccctgt tagtgccgta tgacagcccc catcaaatga ccttggccaa gtcacggttt 1260ctctgtggtc aaggttggtt ggctgattgg tggaaagtag ggtggaccaa aggaggccac 1320gtgagcagtc agcaccagtt ctgcaccagc agcgcctccg tcctagtggg tgttcctgtt 1380tctcctggcc ctgggtgggc tagggcctga ttcgggaaga tgcctttgca gggaggggag 1440gataagtggg atctaccaat tgattctggc aaaacaattt ctaagatttt tttgctttat 1500gtgggaaaca gatctaaatc tcattttatg ctgtatttta tatcttagtt gtgtttgaaa 1560acgttttgat ttttggaaac acatcaaaat aaataatggc gtttgttgta aaaaaaaaaa 1620aaaaaaactc grgggggggc ccggtaccca aatcgcc 1657 70 711 DNA Homo sapiens 70ggcacgagcg aagaccctgt tcggaccctg ccccgattcc agactcaggt agatcgtcgg 60cataccctct accgtggaca ccaggcagcc ctggggctga tggagagaga tcaggtatcc 120cccagggagt aggggctacc ttgaggggat gatagacctc ccccactccc agtgkkactc 180tggaaatatg aaggaactag ggagtggaag agatttcaga gctggggaga ggagttcctc 240ccttcaaagc cagcaactgc ctttggggaa tgtcgggggg tctctccttt ctcctgcttg 300tgtkargtgg tacacagtcc ccccttcacc tggcgggaag ctgtcccgga cagactcatc 360tcagctttcc cttggggcag gatcgggggc agcagctcca gcagaaacag caggatctgg 420agcaggaagg cctcgaggcc acacaggggc tgctggccgg cgagtgggcc ccacccctct 480ggragctggg cagcctcttc caggccttcg tgaagaggga gagccaggct tatgcgtaag 540cttcatagct tctgctggcc tggggtggac ccaggacccc tggggcctgg gtgccctgag 600tggtggtaaa gtggagcaat cccttcacgc tccttggcca tgttctgagc ggccagcttg 660gcctttgcct taataaatgt gctttatttt caaaaaaaaa aaaaaaaaac t 711 71 935 DNAHomo sapiens misc_feature (510) n equals a,t,g, or c 71 ggcacagggtgaaagccagc taaaccccaa gtggagaagt gaaagacatg gttgttccca 60 taagtttattgctcacatta tgaaagaagc catagtcatg agtgaaccac tccctaggtt 120 gataaggaaaccaacacgga agatctcttt ctggaagaag cagccagcct cgtgaaggag 180 cggcccagccgccgggcccg agggtcgcct tttgttcgga gtggcacgat tgtccgttcc 240 cagacattctcgcctggagc acgaagccag tatgtttgca gactttatcg tagtgacagc 300 gacagttcaacgctgccccg gaagtccccc tttgtccgaa atactttgga aagacgaacc 360 cttcgctataagcagtcatg caggtcttcc ctggctgagc tcatggcccg cacctccctg 420 gacttggagctggatctcca ggcgtcgaga acacggcaga ggcagctgaa tgaggagctc 480 tgcgccctccgtgagctgcg gcagcggttn ggaggacgcc cagctccgtg gccagactga 540 cctcccaccctgggtgcttc gggacgagcg gctccgtggc ctgctgcggg agccgagcgg 600 cagacaagacagaccaaact tgactaccgt catgagcagg cggctgagaa gatgctgaag 660 aaggcctccaaggagatcta ccagctgcgt ggcagagcca caaagagccc atccaagtgc 720 agacctttagggagaagata gcattcttca caaggccaag gatcaacata cctcctctcc 780 cagccgacgacgtctgatgg agtgcattgt gcacatgaag tatttatcca cctgttttat 840 tttcatgaagttcttagact agctgaattt gtctttaaaa tatttgtgca aagctattaa 900 tatacacattttgtaaaaaa aaaaaaaaaa aaact 935 72 504 DNA Homo sapiens misc_feature(504) n equals a,t,g, or c 72 gcaggggcga ggggytgggg accgcggggcggacgggagc gagtatgtcc gctctgactc 60 ggctggcgtc tttcgctcgc gttggaggccgccttttcag aagcggctgc gcacggactg 120 ctggagatgg tggagtccgt catgccggtggtggtgtgca cattgagccc cggtatagac 180 agttccccca gctgaccaga tcccaggtgttccagagcga gttcttcagc ggactcatgt 240 ggttctggat tctctggcgc ttttggcatgactcagaaga ggtgctgggt cactttccgt 300 atcctgatcc ttcccagtgg acagatgaagaattaggtat ccctcctgat gatgaagact 360 gaaggtgtag actcagcctc actctgtacaagagccaggt gagaatttca aggattatcg 420 acttcatatt gcacattaaa gttacaaattaaagtggctt ggtcaagaat garaaaaaaa 480 aaaaaaaatt gggggggggc cccn 504 73620 DNA Homo sapiens 73 gaattcggca cgaggaggag gggaggcggg gtaagtttggtgggaaactc tgtaatttcc 60 wtttttactt tcacagcaat agtgcagaat ccagaatggatgtcctcttt gtagccatct 120 ttgctgtgcc acttatcctg ggacaagaat atgaggatgaagaaagactg ggagaggatg 180 aatattatca ggtggtctat tattatacag tcacccccagttatgatgac tttagtgcag 240 atttcaccat tgattactcc atatttgagt cagaggacaggctgaacagg ttggataagg 300 acataacaga agcaatagag actaccatta gtcttgaaacagcacgtgca gaccatccga 360 agcctgtaac tgtgaaacca gtaacaacgg aacctcagagtccagatctg aacgatgccg 420 tgtccagttt gcgaagtcct attcccctcc tcctgtcgtgtgcctttgtt caggtgggga 480 tgtatttcat gtagaaggtg gaagaaggct gctatgactctttggatggg agtctggcaa 540 gaggaaattg gaagataaaa taaataataa gtgaaataaaaaaaaaaaaa aaaaactcga 600 gggggggccc ggtacccaat 620 74 581 DNA Homosapiens 74 acaaggtgtg tgtaaagttt atgtttgtaa actgaattct atcttaaatccaaaaagaac 60 tcgggagtaa ttcatttttg tagcataaag atccctaagt tttattttgaaatatctgat 120 ttttacacgt taaaaaataa cagggcatcg agaggattcc taggtgacatccagactcct 180 ttagctttgt gtgtgtggca ccggttagtc tgcttctctc tcctttcttgcactgcttca 240 cacagccatg ccctgccagc ccgggcaggt gccttcctgt caatgtacatttgggcttct 300 gctcatgctg ccctccctcc cctcccctgc ctcccaaccc cgccccttttgttcctccat 360 ggagtacttc catgggtgtg cctcccccag ccaagccata ataggtggtttccccttcgc 420 ttctgtagcc cttgcagaca tcctctgttt acagtaggtg ttgacttacttcccctctcc 480 ccgstaaagc cataaactcc ttaaggacag gtagcattct tagtatcttcgttcttctca 540 atgaccagta gaccattaaa catgtagcaa acaaatgtga a 581 75 1843DNA Homo sapiens misc_feature (10) n equals a,t,g, or c 75 aaacccaacnccctccggtc cccnaaagaa agcccagccc aaatcccaag ccggcagtga 60 gcccgcgaacaaggccctca agacgcccag ncgaacaagc agcccccagg aggccccgca 120 agagaactccctggcggccc aagcgggcag cttctgtgcg gcagaactca gccaccgaga 180 gcgcagacagcatcgagatt tatgtcccgg agncccagac caggctctga gaccatgcag 240 gaggaaagaaacgattttaa atcattaaaa acacaaaaac taagtgcgaa cggaacagag 300 ttttctcaacctttgctatg gttattctgt ctagagaccc tgagccaact ttcaaattga 360 cgcatacaagggctcacaat ttggcttttt tgggtccctc ccagctttag gttatgaaga 420 ttttactcacaaaaaaaatc aacaaaaatc acgaaactag aaaacttttt ttttcctctt 480 gctggccgtggtggactaga tagatggacg tcggcaactc ccggcccagc ctccatactg 540 cggtctttttactcgttcta tctgatgaga actcacacta gcttgtttac aagatgacga 600 cagtccaagggcagccttgg gcacctgcca tgtccctcct ttccccagct atccccgctc 660 tgaccttgattttcattctt atgtttttct cttttccctt cagagctcac acagtggtca 720 ccattgtggcaagcggcttt ctgggtctca gccctctctg cggttgaggg cccagaggac 780 agagagatggacatgcgtcc cctccctccc cccgccaagt gctcacacac aacctcacgc 840 gcacacacacacacgcagat ggaggcgcct cactgggagg tgccccgcca gccctgggca 900 gtgtcaggcaggactcactc accgctgagc agatgagaga agttttagtc ttggcgggtg 960 gaaatgagacgaagccacag ttatcacact ccagactcct gcccttttat tttctccagc 1020 cccttcttccttcagcaaaa tctaggactc ccgagtggct tccagggggc cgtcagtcct 1080 cagccgcgcctgtgtccggt gcccgagggg cgggcggcgg tgtctgtatg tatgtgtaca 1140 tatgcacatagaccttagag tgtatagtta acaaacgccc atctgctcac ccatgcccac 1200 ccagcgccgccgccgctggc tctcggggca cctggcagga ggcgggtgtg tgaatagcat 1260 atatttttacatgtactata tctaggtgtg tgtacaagtg tgtgtaaaaa tatatacctt 1320 gtgtgtaagcagcccttttt ttttttggtc tccacccccc tccccccgcc ccgcactcct 1380 aagggcccatctgcccagcc tctgagtttt ctgttctatt ttttttttaa ccccaattat 1440 ccttctctctctcctgcccc cgcatcccac tcccagggtg tcacgagccc tgagctgcaa 1500 tggcccgggcctgcagggcg gggtagggga gggcarggct sagccccgaa gccagctcag 1560 tacctgaggggctgctctat gctgtgtatg cgcctctctg gcatccgaga catcctcttg 1620 gtggcgcttgctngcagggg accccccccc cgtccccagg tgaaccaagg gtctgctccg 1680 gggcccatttccagcttggc cgccgtctgt gaccttgggc aagtcacttg acctctgtgt 1740 gcctcaacttcctcctctgt aaaacgggga cagtccctgc ccctccctac ctcacaggca 1800 tgttgtgagaataaatgagg taacgtgtaa aaaaaaaaaa aat 1843 76 1441 DNA Homo sapiensmisc_feature (1056) n equals a,t,g, or c 76 tcgacccacg cgtccggctccccgagccct gccaaccatg gtgaacttgg gtctgtcccg 60 ggtggacgac gccgtggctgccaagcaccc gggactcggg gagtatgccg catgccagtc 120 acacgccttc atgaagggcgttttcacctt cgtcacaggc accggcatgg cctttggctt 180 gcagatgttc attcagaggaagtttccata ccctttgcag tggagcctcc tagtggccgt 240 ggttgcaggc tctgtggtcagctacggggt gacgagagtg gagtcggaga aatgcaacaa 300 cctctggctc ttcctggagaccgggcagct ccccaaagac aggagcacag atcagagaag 360 ctaggagagc tccagcaggggcacagagga ttgggggcag gaggagtctg gaacacagcc 420 ttcatgcccc ctgaccccaggccgaccctc cccacaccct agggtacccc agtcgtatcc 480 tctgtccgca tgtktggccaggcctgacaa acacctgcag atggctgctg ccccaacctg 540 ggacctgccc agraggttggagcagaaagg gctctccctg gggtggtgtt tctcctctag 600 ggtattggga tgcatgttctgcactgccag cagagagggt gtgtctgggg gccaccacct 660 atgggacacg gggtcgaaggggcctgtaca ctctgtcatt tcctttctag cccctgcatc 720 tccaacaagt ccaaggtgacagctggtgct aggggcgtgg ggttaataaa tggcttatcc 780 ttctctccac ccaagtttccacctgaccag gtgaaaaaca aatcagaagg gtaagatgat 840 gacaggtcac atgaaacctttattacccta cagttgatat atgaggatca catgcaagtt 900 acatactgag gatgtacagggaagttccca gcgctgaacc ccagaattag acgttcgcat 960 cagccccgta ggccacgtggacaccaccac agcctctctg tatgggggtc tgcctctgta 1020 gcacttggca tgtaggggcagagcaaaagg ggccangctg gccagagcct ggctgctggg 1080 nagargaggg acttgtgggscacgccacnt gcctatcatt ccccaytcat ctattagcca 1140 aagtcactcc ccagaggcagagctagcccg ttgtagccgt gtctgtgtgg agggaaagct 1200 tctgagtggg caagcctacacacagccccg agccccaaga ggaggaagag gtggagacca 1260 gacggaacct ccacaagtccatcatggtta cagctggctt ccccgcagca ccgaagaccc 1320 acagcatngg ccctgctgcccccgacccag ctcagctgcc angcctcacc ttgccaggaa 1380 ttgaaagaaa gttattgagtactaattggc ctcagagtna caggaagctc aagttaaagt 1440 g 1441 77 910 DNA Homosapiens 77 ggcagagctg gccttcgact cgctatgtcc actaacaata tgtcggacccacggaggccg 60 aacaaagtgc tgaggtgagg accccagcgt cgtgggcacg ggttcgggttgtgggtgtgg 120 atcggggccc tgggaagcgc ctgtctatcc cgggggcagg acctgagcgcccctgaccct 180 cgagcctgtc gcaggtacaa gcccccgccg agcgaatgta acccggccttggacgacccg 240 acgccggact acatgaacct gctgggcatg atcttcagca tgtgcggcctcatgcttaag 300 ctgaagtggt gtgcttgggt cgctgtctac tgctccttca tcagctttgccaactctcgg 360 agctcggagg acacgaagca aatgatgagt agcttcatgt gagacttgccctacagaaca 420 agtgactctt gagtaagggg tggggggacc ccagcctggc catcctagactgacacctct 480 ctcctgtctt catgctgtcc atctctgccg tggtgatgtc ctatctgcagaatcctcagc 540 ccatgacgcc cccatggtga taccagccta gaagggtcac attttggaccctgtctatcc 600 actaggcctg ggctttggct gctaaacctg ctgccttcag ctgccatcctggacttccct 660 gaatgaggcc gtctcggtgc ccccagctgg atagagggaa cctggccctttcctagggaa 720 caccctaggc ttacccctcc tgcctccctt cccctgcctg ctgctgggggagatgctgtc 780 catgtttcta ggggtattca tttgctttct cgttgaaacc tgttgttaataaagtttttc 840 actctgaaaa aaaaaaaaaa aaaaaaaaac tygrgggggg gcccggaacccaattcsccg 900 gatagtgagt 910 78 2776 DNA Homo sapiens 78 tcgacccacgcgtccgggcg ggcagtgatg gcggctggtg atggggacgt gaagctaggc 60 accctggggagtggcagcga gagcagcaac gacggcggca gcgagagtcc aggcgacgcg 120 ggagcggcagcgraaggggg aggctgggcg gcggcggcgt tggcgcttct gacggggggc 180 ggggaaatgctgctgaacgt ggcgctggtg gctctggtgc tgctgggggc ctaccggctg 240 tgggtgcgctgggggcggcg gggtctgggg gccggggccg gggcgggcga ggagagcccc 300 gccacctctctgcctcgcat gaagaagcgg gacttcagct tggagcagct gcgccagtac 360 gacggctcccgcaacccgcg catcctgctc gcggtcaatg ggaaagtctt cgacgtgacc 420 aaaggcagcaagttctacgg cccggcgggt ccatatggaa tatttgctgg tagggatgcc 480 tccagaggactggccacatt ttgcctagat aaagatgcac ttagagatga atatgatgat 540 ctctcagatttgaatgcagt acaaatggag agtgttcgag aatgggaaat gcagtttaaa 600 gaaaaatatgattatgtagg cagactccta aaaccaggag aagaaccatc agaatataca 660 gatgaagaagataccaagga tcacaataaa caggattgaa ctttgtaaac aaccaaagtc 720 aggggccttcagaactgcaa ttcttactcc ctttcacaga ctgtccggag tctttgggtt 780 tgattcacctgctgcgaaaa acattcaaca aattgtgtac aagataaatt aatctcacta 840 tgaagatttgaataactaga cattatttat gctgccaaac tcatttgttg cagttgtttg 900 taatgtctagtggggcttca tcatcctgaa aagaaggaga cagggatttt tttaaagagc 960 aagaaagtcacaatattact tctttccttc cttttttcct tctttccttt cttctttctc 1020 tttctttctttttaaaatat attgaagaca accagatatg tatttgctac tcaagtgtac 1080 agatctcctcaagaaacatc aagggactcc tgtgtcacat actgtgtttt tattttaaca 1140 tgggtgagggaggcgacctg atcaggggag gtgggggtac acatcaattt gagttgttca 1200 ggctactgaaacattaaaat gtgaattccc aaacttttct ttttggcttt gtcagggaaa 1260 agaaaaatatctttataaag aaatctttgg aaattaggag aaggaatttc aggtgggttt 1320 aagtcagagctagttcccca acagaaagat catttgaaac cagtttttat cccttctctt 1380 tccttccctttccctaaatc aaatcaatat taattgtgcc ttatttcact taacatagac 1440 ttgaattatttttagggaaa gcccctataa tgaattcaga aatcactaca agcagcatta 1500 agactgaagttggaatattc tgttgaccat aaaaccttga tatcattctg tgtatataga 1560 atgtaaaaggaatattacag tgttaactgc catatatgta atatacacaa actcaattag 1620 cattgtaatggccaaatgca ttcccccatg cttttctgtt ttcaaaaaaa ttgaaaaaca 1680 aatcaactcttatccccaac agctgcctaa ttttaggagt ctgaccctcc acatctcact 1740 ggtgtgggtgcatggggctg tggagtgggt gtcagtatgg atgtgtctga atgtgtgagg 1800 ccttggaagggactctttct gcagatactg taaatacaag taccatttta ataaagcatg 1860 tacaataaaccaaaataagc ttgagttgga ctttatatac agaactgtaa gccagtgcat 1920 tatgatacagttgtaagatt gtgcatttga ttcaagataa ggaaaaatct tggaaatgaa 1980 aagcaggcackggttaacca agttgtacac attgtaccac attcagcata actttaggaa 2040 gaaattccactttgtgaaca ttctccagaa atccaagatt attcaggtaa gaattggtat 2100 attaaatgtacatcttttta ctttctattt tgatgccaac tgattatact agacaattag 2160 cactccaggtggttattgaa cacaaaacag taaaagaata ttgcactgat agatactaaa 2220 ttattattttattaggttga aaaagccctt actaaaagcc cctcatatat caattacttt 2280 atttcattatgactacttag gttccgggct ggggacaagt tcacttaaaa aggcaatgtt 2340 atttaacaggtcaccagtta agacttctgc tttgtagata catgcagaag ccatcaaaca 2400 agggggrgcttttaactgca acaataagct aaagtatgta aaatactaca ttctattcag 2460 tcttggagtgttttgtagaa agttatcttc agccaaatct ttgctgaaga ctggttgtgg 2520 agtgttggtaaatgctttgt gtttttatgt aaaatatttt ctaaacaaaa aatgttaaaa 2580 gtacatgtcctctgtagtaa actgatatct atatatatga atcattcaag cctaaagtct 2640 agtaataaactgtacttgtg aatagagaaa ccctaaatat tcatgcagwa aaaattatgc 2700 ggtctgttaagaaaaatgag taatttgtgt tttggacttg aaataaacag tgttctgtag 2760 ataattcctcaacttc 2776 79 1487 DNA Homo sapiens misc_feature (78) n equals a,t,g,or c 79 ccgctgctga taactatggc atcccccggg cctgcaggaa ttcggcacggagctacggcg 60 ccgcctggct cctgctgnca cctgcaggct cgtcgcgggt ggagcccacccaagacatca 120 gcatcagcga ccagctgggg ggccaggacg tgcccgtgtt ccggaacctgtccctgctgg 180 tggtgggtgt cggcgccgtg ttctcactgc tattccacct gggcacccgggagaggcgcc 240 ggccgcatgc ggasgagcca ggcgagcaca cccccctgtt ggcccctgccacggcccagc 300 ccctgctgct ctggaagcac tggctccggg agcsggcttt ctaccaggtgggcatactgt 360 acatgaccac caggctcatc gtgaacctgt cccagaccta catggccatgtacctcacct 420 actcgctcca cctgcccaag aagttcatcg cgaccattcc cctggtgatgtacctcagcg 480 gcttcttgtc ctccttcctc atgaagccca tcaacaagtg cattgggaggaacatgacct 540 acttctcagg cctcctggtg atcctggcct ttgccgcctg ggtggcgctggcggagggac 600 tgggtgtggc cgtgtacgca gcggctgtgc tgctgggtgc tggctgtgccaccatcctcg 660 tcacctcgct ggccatgacg gccgacctca tcggtcccca cacgaacagcggagckttcg 720 tgtacggctc catgagcttc ttggataagg tggccaatgg gctggcagtcatggccatcc 780 agagcctgca cccttgcccc tcagagctct gctgcagggc ctgcgtgagcttttaccact 840 gggcgatggt ggctgtgacg ggcggcgtgg gcgtggccgc tgccctgtgtctctgtagcc 900 tcctgctgtg gccgacccgc ctgcgacgct gatgagacct gcacgcantggctcacagca 960 gcacgatttg tgacagcccg aggcggagaa caccgaacac ccagtgaaggtgaggggatc 1020 agcacggcgc ggccacccac gcacccacgc gctggaatga gactcagccacaaggaggtg 1080 cgaagctctg acccaggcca cagtgcggat gcaccttgag gatgtcacgctcagtgagag 1140 acaccagaca cagaagggta cgctgtgatc ccacttctat gaaatgtccaggacagacca 1200 atccacagaa tcagggagag gattcgtggg tgccgggact ggggagggggacctgggggt 1260 gactaggtga cataatgggg acagggctgc cttctgggtg atgagaatgttctggaatca 1320 gatgggatgg ctgcacggcg tggtgaaggt actgaacgcc acctcactgtaagacggtag 1380 attttgtatt ttaccacaat aaacaaaaca aaacaaaacc aaaaaaaaaaaaaaaaaaaa 1440 aaaaaaaagg aattcgatat caagcttatc gataccgtcg acctcga 148780 1563 DNA Homo sapiens misc_feature (14) n equals a,t,g, or c 80aattcggcac gagncagaaa cctgcggaaa atggtagcga tggcggctgg gccgagtggg 60tgtctggtgc cggcgtttgg gctacggttg ttgttggcga ctgtgcttca agcggtgtct 120gcttttgggg cagagttttc atcggaggca tgcagagagt taggcttttc tagcaacttg 180ctttgcagct cttgtgatct tctcggacag ttcaacctgc ttcagctgga tcctgattgc 240agaggatgct gtcaggagga agcacaattt gaaaccaaaa agctgtatgc aggagctatt 300cttgaagttt gtggatgaaa attgggaagg ttccctcaag tccaagcttt tgttaggagt 360gataaaccca aactgttcag aggactgcaa atcaagtatg tccgtggttc agaccctgta 420ttaaagcttt tggacgacaa tgggaacatt gctgaagaac tgagcattct caaatggaac 480acagacagtg tagaagaatt cctgagtgaa aagttggaac gcatataaat cttgcttaaa 540ttttgtccta tccttttgtt accttatcaa atgaaatatt acagcaccta gaaaataatt 600tagttttgct tgcttccatt gatcagtctt ttacttgagg cattaaatat ctaattaaat 660cgtgaaatgg cagtatagtc catgatatct aaggagttgg caagcttaac aaaacccatt 720ttttataaat gtccatcctc ctgcatttgt tgataccact aacaaaatgc tttgtaacag 780acttgcggtt aattatgcaa atgatagttt gtgataattg gtccagtttt acgaacaaca 840gatttctaaa ttagagaggt taacaagaca gatgattact atgcctcatg tgctgtgtgc 900tctttgaaag gaatgacagc agactacaaa gcaaataaga tatactgagc ctcaacagat 960tgcctgctcc tcagagtctc tcctattttt gtattaccca gctttctttt taatacaaat 1020gttatttata gtttacaatg aatgcactgc ataaaaactt tgtagcttca ttattgtaaa 1080acatattcaa gatcctacag taagagtgaa acattcacaa agatttgcgt taatgaagac 1140tacacagaaa acctttctag ggatttgtgt ggatcagata catacttggc aaatttttga 1200gttttacatt cttacagaaa agtccattta aaagtgatca tttgtaagac caaaatataa 1260ataaaaagtt tcaaaaatct atctgaattt ggaattcttc tggtttgttc tttcatgttt 1320aaaaatgatg tttttcaatg catttttttc atgtaagccc tttttttagc caaaatgtaa 1380aaatggctgt aatatttaaa acttataaca tcttattgtt ggtaatagtg ctttatattt 1440gtctgatttt atttttcaaa gttttttcat ttatgaacac attttcattg gtatattatt 1500taaggaatat ctcttgatat agaattttta tattaaaaat gatttttctt tgcttaaaaa 1560aaa 1563 81 1020 DNA Homo sapiens misc_feature (20) n equals a,t,g, or c81 tgcacgctgg ccatgtgggn gttgggccac tgcgaccccc ggcgctgcac gggccgcaag 60ctggcccgcc tggggctggt gcgctgcctg cgcctgggcc acagattcgg cggtctggtg 120ctgagccccg tgggcaagca gtacgcgtcc cccgcagaca gacagctggt ggcgcagtct 180ggggtcgccg tcatcgactg ctcctgggcc aggctggacg agacaccgtt tgggaagatg 240cgagggagcc acttgcgcct gttgccctac ctggtggccg ccaaccccgt gaactatggc 300cggccctaca gactttcctg cgtggaagcg tttgctgcca ccttctgcat cgtaggcttt 360ccagaccttg ctgtcatttt gctgcggaag tttaaatggg gcaagggctt cttggacctg 420aaccgccagc tcctggacaa gtacgcggcc tgcggcagcc cggaggaggt gctgcaggcg 480gagcaggagt tcttggccaa tgccaaggag agcccccagg aggaggagat cgatcccttc 540gatgtggatt cagggagaga gtttggaaac cccaacaggc ctgtggccag cacccggctg 600ccctcggaca ctgatgacag tgatgcgtct gaggacccag ggcctkgcgc cgagcgcgga 660ggagccagca gcagctgctg tgaagaggag cagacgcagg gacggggggc tgaggccagg 720gccccggctg aggtttggaa aggaatcaag aaacggcaga gagactgagg gttgcagaca 780catatatttt tgaggctggg tgacgagaaa atctagagac atgagggaca taaatgggcc 840tggcagcctc ggctctttgc ggctgctggc aggactgagc tgtccgggtt ctccccacac 900ttccagcaca gctgtgctct gtgtcctgcc tcggcgctct cgcaaatgaa gctgcaggcc 960aagaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaag gggggggggc 102082 770 DNA Homo sapiens misc_feature (757) n equals a,t,g, or c 82tcgacccacg cgtccgggcc gccgtagcgc gtcttgggtc tcccggctgc cgctgctgcc 60gccgccgcct cgggtcgtgg agccaggagc gacgtcaccg ccatggcagg catcaaagct 120ttgattagtt tgtcctttgg aggagcaatc ggactgatgt ttttratgct tggatgtgcc 180cttccaatat acaacaaata ctggcccctc tttgttctat ttttttacat cctttcacct 240attccatact gcatagcaag aagattagtg gatgatacag atgctatgag taacgcttgt 300aaggaacttg ccatctttct tacaacgggc attgtcgtgt cagcttttgg actccctatt 360gtatttgcca gagcacatct gattgagtgg ggagcttgtg cacttgttct cacaggaaac 420acagtcatct ttgcaactat actaggcttt ttcttggtct ttggaagcaa tgacgacttc 480agctggcagc agtggtgaaa agaaattact gaactattgt caaatggact tcctgtcatt 540tgttggccat tcacgcacac aggagatggg gcagttaatg ctgaatggta tagcaagcct 600cttgggggta ttttaggtgc tcccttctca cttttattgt aagcatacta ttttcacaga 660gacttgctga aggattaaaa ggattttctc ttttggaaaa aaaaaaaaaa aaaaacycga 720gggggggccc gtwcccattc scccyatatg aattccnttt ttacaatccc 770 83 481 DNAHomo sapiens misc_feature (322) n equals a,t,g, or c 83 gaattcggcacgagcatagt gttaaccact agaattcact gcccttccta tccaaaaatg 60 acactactgatcatttttct tccttttsct tttacaacat tmacaaattc aggtggctct 120 ttcccagtacggtaggctga ttcgtatgga tgcaccacgg ttggtgactc cccccacccc 180 acagagtttctggcgttcat tcggttgaac ccaaggccag caagggctga ctgggaacaa 240 accgaacactaggccgtgaa ccaatcgtct ctccgtgccc gggagcgamc ccgggggcct 300 ttcactctcccaaggactcc angggggggc cgggtaccca attccgcccc tatagtgaat 360 ccgtnattacaattccacnt gggccgtccn tttttacaaa cgttccgttg aactgggaaa 420 aaccccttggcggtttaccc caactttaat ccgcctttgc aagcacatcc cccccctttt 480 c 481 84 644DNA Homo sapiens 84 gctgggatag agcatgaaag gagaactgct cccttttctgtttctcacag tttggttatg 60 gctttataaa cttktatttg gtgaaagccc cagatacccaaatgtcattg gcaaaactta 120 tttttttttc tggacagatc agatttctag agagagcagatttctagaga gattagcatt 180 catagtaagt gaaaattgtc taattttttt aatccatgctattactgggc agtaggtcta 240 attttttttg acaaaaaata gatctatttt ccttatatattgatttagaa tcttaagtta 300 gaattttata gaagaaatgt ctgagcagtt ctatgtatggaggagcaatt cagcttttca 360 gcagcaactt tatcttttgc cactagaggg agatctgtggttgctttctc ctttggagaa 420 tagctgcttt gcttttattt ttaatttcta aggttggaatagaacttatt ctcaaaattc 480 ctttagtgtt attaaatatt ttcatttatt agtcaaaggtaagttaatta agcttgttta 540 atgatgccaa tcttatgctt ttctgtaatc ttcaatttttaataaatgtg agttagatac 600 taagtgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaaaaaa 644 85 1351 DNA Homo sapiens misc_feature (133) n equals a,t,g, orc 85 ggcacgagtg cgcasgcgtg gggctctctc cttgtcagtc ggcgccgcgt gcgggctggt60 ggctctgtgg cagcggcggc ggcaggactc cggcactatg agcggcttca gcaccgagga 120gcgcgccgcg ccnttctccc tggagtaccg agtcttcctc aaaaatgaga aaggacaata 180tatatctcca tttcatgata ttccaattta tgcagataag gatgtgtttc acatggtagt 240tgaagtacca cgctggtcta atgcaaaaat ggagattgct acaaaggacc ctttaaaccc 300tattaaacaa gatgtgaaaa aaggaaaact tcgctatgtt gcgaatttgt tcccgtataa 360aggatatatc tggaactatg gtgccatccc tcagacttgg gaagacccag ggcacaatga 420taaacatact ggctgttgtg gtgacaatga cccaattgat gtgtgtgaaa ttggaagcaa 480ggtatgtgca agaggtgaaa taattggcgt gaaagttcta ggcatattgg ctatgattga 540cgaaggggaa accgactgga aagtcattgc cattaatgtg gatgatcctg atgcagccaa 600ttataatgat atcaatgatg tcaaacggct gaaacctggc tacttagaag ctactgtgga 660ctggtttaga aggtataagg ttcctgatgg aaaaccagaa aatgagtttg cgtttaatgc 720agaatttaaa gataaggact ttgccattga tattattaaa agcactcatg accattggaa 780agcattagtg actaagaaaa cgaatggaaa aggaatcagt tgcatgaata caactttgtc 840tgagagcccc ttcaagtgtg atcctgatgc tgccagagcc attgtggatg ctttaccacc 900accctgtgaa tctgcctgca cagtaccaac agacgtggat aagtggttcc atcaccagaa 960aaactaatga gatttctctg gaatacaagc tgatattgct acatcgtgtt catctggatg 1020tattagaagt aaaagtagta gcttttcaaa gctttaaatt tgtagaactc atctaactaa 1080agtaaattct gctgtgacta atccaatata ctcagaatgt tatccatcta aagcattttt 1140catatctcaa ctaagataac ttttagcaca tgcttaaata tcaaagcagt tgtcatttgg 1200aagtcacttg tgaatagatg tgcaagggga gcacatattg gatgtatatg ttaccatatg 1260ttaggaaata aaattatttt gctgaaaaaa aaaaaaaaaa aaccncgggg ggggccccgg 1320tccccatttg gccctttggg gggnggtttt a 1351 86 2527 DNA Homo sapiens 86ctcttgctac cttcccggcg cagagaaccc cggctgctca gcgcgctccg gggtcatgga 60gatccccggg agcctgtgca agaaagtcaa gctgagcaat aacgcgcaga actggggaat 120gcagagagca accaatgtca cctaccaagc ccatcatgtc agcaggaaca agagaggtca 180ggtggtgggg accagaggtg gctttcgtgg ttgcacagtt tggctaacag gcttgtctgg 240agcgggaaag actactgtga gcatggcctt ggaggagtac ctggtttgtc atggtattcc 300atgctacact ctggatggtg acaatattcg tcaaggtctc aataaaaatc ttggctttag 360tcctgaagac agagaagaga atgttcgacg catcgcagaa gttgctaaac tgtttgcaga 420tgctggctta gtgtgcatca caagtttcat atcaccttac actcaggatc gcaacaatgc 480aaggcaaatt catgaaggtg caagtttacc gttttttgaa gtatttgttg atgctcctct 540gcatgtttgt gaacagaggg atgtcaaagg actctacaaa aaagcccggg caggagaaat 600taaaggtttc actgggatcg attctgaata tgaaaagcca gaggcccctg agttggtgct 660gaaaacagac tcctgtgatg taaatgactg tgtccagcaa gttgtggaac ttctacagga 720acgggatatt gtacctgtgg atgcatctta tgaagtaaaa gaactatatg tgccagaaaa 780taaacttcat ttggcaaaaa cagatgcgga aacattacca gcactgaaaa ttaataaagt 840ggatatgcag tgggtgcagg ttttggcaga aggttgggca accccattga atggctttat 900gagagagagg gagtacttgc agtgccttca ttttgattgt cttctggatg gaggtgtcat 960taacttgtca gtacctatag ttctgactgc gactcatgaa gataaagaga ggctggacgg 1020ctgtacagca tttgctctga tgtatgaggg ccgccgtgtg gccattcttc gcaatccaga 1080gttttttgag cacaggaaag aggagcgctg tgccagacag tggggaacga catgcaagaa 1140ccacccctat attaagatgg tgatggaaca aggagattgg ctgattggag gagatcttca 1200agtcttggat cgagtttatt ggaatgatgg tcttgatcag tatcgtctta ctcctactga 1260gctaaagcag aaatttaaag atatgaatgc tgatgctgtc tttgcatttc aactacgcaa 1320cccagtgcac aatggacatg ccctgttaat gcaggatacc cataagcaac ttctagagag 1380gggctaccgg cgccctgtcc tcctcctcca ccctctgggt ggctggacaa aggatgacga 1440tgttcctttg atgtggcgta tgaagcagca tgctgcagtg ttggaggaag gagttctgaa 1500tcctgagacg acagtggtgg ccatcttccc atctcccatg atgtatgctg gaccaactga 1560ggtccagtgg cattgcagag cacggatggt tgcaggagcc aacttttaca ttgttggacg 1620agaccctgct ggcatgcctc atccagaaac agggaaggat ctttatgagc caagtcatgg 1680tgccaaagtg ctgacgatgg cccctggttt aatcactttg gaaatagttc cctttcgagt 1740tgcagcttac aacaagaaaa agaagcgtat ggactactat gactctgaac accatgaaga 1800ctttgaattt atttcaggaa cacgaatgcg caaacttgct cgagaaggcc agaaaccacc 1860tgaaggtttc atggctccca aggcttggac cgtgctgaca gaatactaca aatccttgga 1920gaaagcttag gctgttaacc cagtcactcc acctttgaca cattactagt aacaagaggg 1980gaccacatag tctctgttgg catttctttg tggtgtctgt ctggacatgc ttcctaaaaa 2040cagaccattt tccttaactt gcatcagttt tggtctgcct tatgagttct gttttgaaca 2100agtgtaacac actgatggtt ttaatgtatc ttttccactt attatagtta tattcctaca 2160atacaatttt aaaattgtct ttttatatta tatttatgct tctgtgtcat gattttttca 2220agctgttata ttagttgtaa ccagtagtat tcacattaaa tcttgctttt tttcccctta 2280aaaaaagaaa aaaattacca aacaataaac ttggctagac cttgttttga ggattttaca 2340agacctttgt agcgattaga ttttttttct acattgaaaa tagaaactgc ttcctttctt 2400ctttccagtc agctattggt ctttccagct gttataatct aaagtattct tatgatctgt 2460gtaagctctg aatgaacttc tttactcaat aaaattaatt ttttggcttc ttaaaaaaaa 2520aaaaaaa 2527 87 2566 DNA Homo sapiens misc_feature (22) n equals a,t,g,or c 87 cccaagaatt cggcacgagc gnggcawaak tgggatttct gaaacctgtaggccccaagc 60 ccatcaactt gcccaaagaa gattccaaac ctacatttcc ctggcctsctggaaacaagc 120 catctcttca cagtgtaaac caagaccatg acttaaagcc actaggccgaaatctgggcc 180 tactcctcca acctcagaaa atgaacagaa gcaagckttt cccaaattgactggggttaa 240 agggaaattt atgtcagcat cacaagatct tgaacccaag cccctcttccccaaacccgc 300 ctttggccag aagccgcccc taagtaccga gaactcccat gaagacgaaagccccatgaa 360 gaatgtgtct tcatcaaaag ggtccccagc tcccctggga gtcaggtccaaaagcggccc 420 tttaaaacca gcaagggaag actcagaaaa taaagaccat gcaggggagatttcaagttt 480 gccctttcct ggagtggttt tgaaacctgc tgcgagcagg ggaggcccaggtctctccaa 540 aaatggtgaa gaaaaaaagg aagataggaa gatagatgct gctaagaacaccttccagag 600 caaaataaat caggaagagt tggcctcagg gactcctcct gccaggttccctaaggcccc 660 ttctaagctg acagtggggg ggccatgggg ccaaagtcag gaaaaggaaaagggagacaa 720 gaattcagcc accccgaaac agaagccatt gcctcccttg tttaccttgggtccacctcc 780 accaaaaccc aacagaccac caaatgttga cctgacgaaa ttccacaaaacctcttctgg 840 aaacagtact agcaaaggcc agacgtctta ctcaacaact tccctgccaccacctccacc 900 atcccatccg gccagccaac caccattgcc agcatctcac ccatcacaaccaccagtccc 960 aagcctacct cccagaaaca ttaaacctcc gtttgaccta aaaagccctgtcaatgaaga 1020 caatcaagat ggtgtcacgc actctgatgg tgctggaaat ctagatgaggaacaagacag 1080 tgaaggagaa acatatgaag acatagaagc atccaaagaa agagagaagaaaagggaaaa 1140 ggaagaaaag aagaggttag agctggagaa aaaggaacag aaagagaaagaaaagaaaga 1200 acaagaaata aagaagaaat ttaaactaac aggccctatt caagtcatccatcttgcaaa 1260 agcttgttgt gatgtcaaag gaggaaagaa tgaactgagc ttcaagcaaggagagcaaat 1320 tgaaatcatc cgcatcacag acaacccaga aggaaaatgg ttgggcagaacagcaagggg 1380 ttcatatggc tatattaaaa caactgctgt agagattgac tatgattctttgaaactgaa 1440 aaaagactct cttggtgccc cttcaagacc tattgaagat gaccaagaagtatatgatga 1500 tgttgcagag caggatgata ttagcagcca cagtcagagt ggaagtggagggatattccc 1560 tccaccacca gatgatgaca tttatgatgg gattgaagag gaagatgctgatgatggctc 1620 cacactacag gttcaagaga agagtaatac gtggtcctgg gggattttgaagatgttaaa 1680 gggaaaagat gacagaaaga aaagtatacg agagaaacct aaagtctctgactcagacaa 1740 taatgaaggt tcatctttcc ctgctcctcc taaacaattg gacatgggagatgaagttta 1800 cgatgatgtg gatacctctg atttccctgt ttcatcagca gagatgagtcaaggaactaa 1860 tgttggaaaa gctaagacag aagaaaagga ccttaagaag ctaaaaaagcagraaaaara 1920 araaaaagac ttcaggaaaa aatttaaata tgatggtgaa attagagtcctatattcaac 1980 taaagttaca acttccataa cttctaaaaa gtggggaacc agagatctacaggtaaaacc 2040 tggtgaatct ctagaagtta tacaaaccac agatgacaca aaagttctctgcagaaatga 2100 agaagggaaa tatggttatg tccttcggag ttacctagcg gacaatgatggagagatcta 2160 tgatgatatt gctgatggct gcatctatga caatgactag cactcaactttggtcattct 2220 gctgtgttca ttaggtgcca atgtgaagtc tggattttaa ttggcatgttattgggtatc 2280 aagaaaatta atgcacaaaa ccacttatta tcatttgtta tgaaatcccaattatcttta 2340 caaagtgttt aaagtttgaa catagaaaat aatctctctg cttaattgttatctcagaag 2400 actacattag tgagatgtaa gaattattaa atattccatt tccgctttggctacaattat 2460 gaagaagttg aaggtacttc ttttagacca ccagtaaata atcctccttcaaaaaataaa 2520 aataaaaaaa aaaaaaaaaa actcgagggg gggcccggta cccaat 256688 540 DNA Homo sapiens 88 gaattcggca cgaggctttc tgtgtcctct gtggctgctttagtgtgcca ccaggggcag 60 acttgggtgg gttgcagcag agatggcatg gccctcaaggtccaagatgt ttactctctt 120 gccggtcctc tgttatctct ggtctttgtg gttgccacagttttcttgga tccaggagtt 180 aaaggcagtc ctgagggatg atggcctcat ctccgcagttgcytggaatg ctgaatttca 240 gacgtgctaa aggagggttg cagacattgt gtggwatgcattcagacccc agatgtgggt 300 gcaggaaggc aggcatggca cagccaggta gagactggtttccaggccca agcagccttc 360 agcagctgtg cgccttgttt ctgatgttgt ttgggagtaagaataatgta gacatggggg 420 gtcatgargc tcaataaaaa cttcaaggaa acctcccatggcatggttgg gcgcagtgac 480 tcatgcctgt aaccccagca ctgtggaatg ccaaggtggaaggatcgctt gaggccaaga 540 89 1863 DNA Homo sapiens misc_feature (1836) nequals a,t,g, or c 89 tcgacccacg cgtccggcga gatccctacc gcagtagccgcctctgccgc cgcggagctt 60 cccgaacctc ttcagccgcc cggagccgct cccggagcccggccgtagag gctgcaatcg 120 cagccgggag cccgcagccc gcgccccgag cccgccgccgcccttcgagg gcgccccagg 180 ccgcgccatg gtgaaggtga cgttcaactc cgctctggcccagaaggagg ccaagaagga 240 cgagcccaag agcggcgagg aggcgctcat catcccccccgacgccgtcg cggtggactg 300 caaggaccca gatgatgtgg taccagttgg ccaaagaagagcctggtgtt ggtgcatgtg 360 ctttggacta gcatttatgc ttgcaggtgt tattctaggaggagcatact tgtacaaata 420 ttttgcactt caaccagatg acgtgtacta ctgtggaataaagtacatca aagatgatgt 480 catcttaaat gagccctctg cagatgcccc agctgctctctaccagacaa ttgaagaaaa 540 tattaaaatc tttgaagaag aagaagttga atttatcagtgtgcctgtcc cagagtttgc 600 agatagtgat cctgccaaca ttgttcatga ctttaacaagaaacttacag cctatttaga 660 tcttaacctg gataagtgct atgtgatccc tctgaacacttccattgtta tgccacccag 720 aaacctactg gagttactta ttaacatcaa ggctggaacctatttgcctc agtcctatct 780 gattcatgag cacatggtta ttactgatcg cattgaaaacattgatcacc tgggtttctt 840 tatttatcga ctgtgtcatg acaaggaaac ttacaaactgcaacgcagag aaactattaa 900 aggtattcag aaacgtgaag ccagcaattg tttcgcaattcggcattttg aaaacaaatt 960 tgccgtggaa actttaattt gttcttgaac agtcaagaaaaacattattg aggaaaatta 1020 atatcacagc ataaccccac cctttacatt ttgtgcagtgattatttttt aaagtcttct 1080 ttcatgtaag tagcaaacag ggctttacta tcttttcatctcattaattc aattaaaacc 1140 attaccttaa aatttttttc tttcgaagtg tggtgtcttttatatttgaa ttagtaactg 1200 tatgaagtca tagataatag tacatgtcac cttaggtagtaggaagaatt acaatttctt 1260 taaatcattt atctggattt ttatgtttta ttagcattttcaagaagacg gattatctag 1320 agaataatca tatatatgca tacgtaaaaa tggaccacagtgacttattt gtagttgtta 1380 gttgccctgc tacctagttt gttagtgcat ttgagcacacattttaattt tcctctaatt 1440 aaaatgtgca gtattttcag tgtcaaatat atttaactatttagagaatg atttccacct 1500 ttatgtttta atatcctagg catctgctgt aataatattttagaaaatgt ttggaattta 1560 agaaataact tgtgttacta atttgtataa cccatatctgtgcaatggaa tataaatatc 1620 acaaagttgt ttaactagac tgcgtgttgt ttttcccgtataataaaacc aaagaatagt 1680 ttggttcttc aaatcttaag agaatccaca taaaagaagaaactattttt taaaaattca 1740 cttctatata tacaatgagt aaaatcacag attttttctttaaataaaaa taagtcattt 1800 taataactaa accagattct ttgtgatact attaangtaacatttagccc caaaaaaaaa 1860 aaa 1863 90 2478 DNA Homo sapiens 90ggcacagcgg cacgaggtga gctgagccgg tgggtgagcg gcggccacgg catcctgtgc 60tgtgggggct acgaggaaag atctaattat catggacctg cgacagtttc ttatgtgcct 120gtccctgtgc acagcctttg ccttgagcaa acccacagaa aagaaggacc gtgtacatca 180tgagcctcag ctcagtgaca aggttcacaa tgatgctcag agttttgatt atgaccatga 240tgccttcttg ggtgctgaag aagcaaagac ctttgatcag ctgacaccag aagagagcaa 300ggaaaggctt ggaaagattg taagtaaaat agatggcgac aaggacgggt ttgtcactgt 360ggatgagctc aaagactgga ttaaatttgc acaaaagcgc tggatttacg aggatgtaga 420gcgacagtgg aaggggcatg acctcaatga ggacggcctc gtttcctggg aggagtataa 480aaatgccacc tacggctacg ttttagatga tccagatcct gatgatggat ttaactataa 540acagatgatg gttagagatg agcggaggtt taaaatggca gacaaggatg gagacctcat 600tgccaccaag gaggagttca cagctttcct gcaccctgag gagtatgact acatgaaaga 660tatagtagta caggaaacaa tggaagatat agataagaat gctgatggtt tcattgatct 720agaagagtat attggtgaca tgtacagcca tgatgggaat actgatgagc cagaatgggt 780aaagacagag cgagagcagt ttgttgagtt tcgggataag aaccgtgatg ggaagatgga 840caaggaagag accaaagact ggatccttcc ctcagactat gatcatgcag aggcagaagc 900caggcacctg gtctatgaat cagaccaaaa caaggatggc aagcttacca aggaggagat 960cgttgacaag tatgacttat ttgttggcag ccaggccaca gattttgggg aggccttagt 1020acggcatgat gagttctgag ctrcggagga accctcattt cctcaaaagt aatttatttt 1080tacagcttct ggtttcacat gaaattgttt gcgctactga gactgttact acaaactttt 1140taagacatga aaaggcgtaa tgaaaaccat cccgtcccca ttcctcctcc tctctgaggg 1200actggaggga agccgtgctt ctgaggaaca actctaatta gtacacttgt gtttgtagat 1260ttacactttg tattatgtat taacatggcg tgtttatttt tgtatttttc tctggttggg 1320agtatgatat gaaggatcaa gatcctcaac tcacacatgt agacaaacat tagctcttta 1380ctctttctca acccctttta tgattttaat aattctcact taactaattt tgtaagcctg 1440agatcaataa gaaatgttca ggagagagga aagaaaaaaa atatatgctc cacaatttat 1500atttagagag agaacactta gtcttgcctg tcaaaaagtc caacatttca taggtagtag 1560gggccacata ttacattcag ttgctatagg tccagcaact gaacctgcca ttacctgggc 1620aaggaaagat ccctttgctc taggaaagct tggcccaaat tgattttctt ctttttcccc 1680ctgtaggact gactgttggc taattttgtc aagcacagct gtggtgggaa gagttagggc 1740cagtgtcttg aaaatcaatc aagtagtgaa tgtgatctct ttgcagagct atagatagaa 1800acagctggaa aactaaagga aaaatacaag tgttttcggg gcatacattt tttttctggg 1860tgtgcatctg ttgaaatgct caagacttaa ttatttgcct tttgaaatca ctgtaaatgc 1920ccccatccgg ttcctcttct tcccaggtgt gccaaggaat taatcttggt ttcactacaa 1980ttaaaattca ctcctttcca atcatgtcat tgaaagtgcc tttaacgaaa gaaatggtca 2040ctgaatggga attctcttaa gaaaccctga gattaaaaaa agactatttg gataacttat 2100aggaaagcct agaacctccc agtagagtgg ggattttttt cttcttccct ttctcttttg 2160gacaatagtt aaattagcag tattagttat gagtttggtt gcagtgttct tatcttgtgg 2220gctgatttcc aaaaaccaca tgctgctgaa tttaccaggg atcctcatac ctcacaatgc 2280aaaccactta ctaccaggcc tttttctgtg tccactggag agcttgagct cacactcaaa 2340gatcagagga cctacagaga gggctctttg gtttgaggac catggcttac ctttcctgcc 2400tttgacccat cacaccccat ttcctcctct ttccctctcc ccgctgccaa ttcctgcagc 2460ccgggggaac cactagtt 2478 91 2058 DNA Homo sapiens misc_feature (69) nequals a,t,g, or c 91 tcggccttgc ttttgtggyc ttcctctgtg gccagagcgttttcatcacc aagcctcctg 60 atggcagtnc cttcaccgat atgttcaaga tactgacgtattcctgctgt tcccagaagc 120 gaagtggaga gcgccagagt aatggtgaag gcattggagtntttcagcaa tcttctaaac 180 aaagtctgtt tgattcatgt aagatgtctc atggtgggccatttacagaa gagaaagtgg 240 aagatgtgaa agctctggtc aagattgtcc ctgttttcttggctttgata ccttactgga 300 cagtgtattt ccaaatgcag acaacatatg ttttacagagtcttcatttg aggattccag 360 aaatttcaaa tattacaacc actcctcaca cgctccctgcagcctggctg accatgtttg 420 atgctgtgct catcctcctg ctcatccctc tgaaggacaaactggtcgat cccattttga 480 gaagacatgg cctgctccca tcctccctga agaggatcgccgtgggcatg ttctttgtca 540 tgtgctcrgc ctttgctgca ggaattttgg agagtaaaaggctgaacctt gttaaagaga 600 aaaccattaa tcagaccatc ggcaacgtcg tctaccatgctgccgatctg tcgctgtggt 660 ggcaggtgcc gcagtacttg ctgattggga tcagcgagatctttgcaagt atcgcaggcc 720 tggaatttgc atactcagct gcccccaagt ccatgcagagtgccataatg ggcttgttct 780 ttttcttctc tggcgtcggg tcgttcgtgg gttctggactgctggcactg gtgtctatca 840 aagccatcgg atggatgagc agtcacacag actttggtaatattaacggc tgctatttga 900 actattactt tttccttctg gctgctattc aaggagctaccctcctgctt ttcctcatta 960 tttctgtgaa atatgaccat catcgagacc atcagcgatcaagagccaat ggcgtgccca 1020 ccagcaggag ggcctgacct tcctgaggcc atgtgcggtttctgaggctg acatgtcagt 1080 aactgactgg ggtgcactga gaacaggcaa gactttaaattcccataaaa tgtctgactt 1140 cactgaaact tgcatgttgc ctggattgat ttcttctttccctctatcca aaggagcttg 1200 gtaagtgcct tactgcagcg tgtctcctgg cacgctgggccctccgggag gagagctgca 1260 gatttcgagt atgtcgcttg tcattcaagg tctctgtgaatcctctagct gggttccctt 1320 ttttacagaa actcacaaat ggagattgca aagtcttggggaactccacg tgttagttgg 1380 catcccagtt tcttaaacaa atagtatcac ctgcttcccatagccatatc tcactgtaaa 1440 aaaaaaaatt aataaactgt tacttatatt taagaaagtgaggatttttt ttttttaaag 1500 ataaaagcat ggtcagatgc tgcaaggatt ttacataaatgccatattta tggtttcctt 1560 cctgagaaca atcttgctct tgccatgttc tttgatttaggctggtagta aacacatttc 1620 atctgctgct tcaaaaagta cttacttttt aaaccatcaacattactttt ctttcttaag 1680 gcaaggcatg cataagagtc atttgagacc atgtgtcccatctcaagcca cagagcaact 1740 cacggggtac ttcacacctt acctagtcag agtgcttatatatagcttta ttttggtacg 1800 attgagacta aagactgatc atggttgtat gtaaggaaaacattcttttg aacagaaata 1860 gtgtaattaa aaataattga aagtgttaaa tgtgaacttgagctgtttga ccagtcacat 1920 ttttgtattg ttactgtacg tgtatctggg gcttctccgtttgttaatac tttttctgta 1980 tttgttgctg tatttttggc ataactttat tataaaaagcatctcaaatg cgaaawaaaa 2040 aaaaaaaaaa aaaaaaac 2058 92 1411 DNA Homosapiens misc_feature (1391) n equals a,t,g, or c 92 ggcacaggagcgacccggga gaaggagggc camgakgcgg aagcggagga gtctccagga 60 gacccggggacagcatcgcc caggcccctg tttgcaggcc tttcagatat atccatctca 120 caagacatccccgtagaagg agaaatcacc attcctatga gatctcgcat ccgggagttt 180 gacagctccacattaaatga atctgttcgc aataccatca tgcgtgatct aaaagctgtt 240 gggaaaaaattcatgcatgt tttgtaccca aggaaaagta atactctttt gagagattgg 300 gatttgtggggccctttgat cctttgtgtg acactcgcat taatgctgca aagagactct 360 gcagatagtgaaaaagatgg agggccccaa tttgcagagg tgtttgtcat tgtctggttt 420 ggtgcagttaccatcaccct caactcaaaa cttcttggag ggaacatatc tttttttcag 480 agcctctgtgtgctgggtta ctgtatactt cccttgacag tagcaatgct gatttgccgg 540 ctggtacttttggctgatcc aggacctgta aacttcatgg ttcggctttt tgtggtgatt 600 gtgatgtttgcctggtctat agttgcctcc acagctttcc ttgctgatag ccagcctcca 660 aaccgcagagccctagctgt ttatcctgtt ttcctgtttt actttgtcat cagttggatg 720 attctcacctttactcctca gtaaatcagg aatgggaaat taaaaaccag tgaattgaaa 780 gcacatctgaaagatgcaat tcaccatgga gctttgtctc tggcccttat ttgtctaatt 840 ttggaggtatttgataactg agtaggtgag gagattaaaa gggagccata tagcactgtc 900 accccttatttgaggaactg atgtttgaaa ggctgttctt ttctctctta atgtcatttc 960 tttaaaaatacatgtgcata ctacacacag tatataatgc ctccttaagg catgatggag 1020 tcaccgtggtccatttgggt gacaaccagt gacttgggaa gcacatagat acatcttaca 1080 agttgaatagagttgataac tattttcagt tttgagaata ccagttcagg tgcagctctt 1140 aaacacattgccttatgact attagaatat gcctctcttt tcataaataa aaatacatgg 1200 tctatatccattttctttta tttctctctc ttaagcttaa aaaggcaatg agagaggtta 1260 ggagtgggttcatacacgga gaatgagaaa acatgcatta accaatattc agattttgat 1320 caggggaaattctayacttg ttgcaaaaaa aaaaaaaaaa aaactcgagg ggggcccggt 1380 acccaatcgcngtatatgat cgnaaacaat c 1411 93 2187 DNA Homo sapiens 93 gctttggctttttttggcgg actggggcgc cctccggaag cgtttccaac tttccagaag 60 tttctcgggacgggcaggag ggggtgggga ctgccatata tagatcccgg gagcagggga 120 gcgggctaagagtagaatcg tgtcgcgctc gagagcgaga gtcacgtccc ggcgctagcc 180 cagcccgacccaggcccacc gtggtgcacg caaaccactt cctggccatg cgctccctcc 240 tgcttctcagcgccttctgc ctcctggagg cggccctggc cgccgaggtg aagaaacctg 300 cagccgcagcagctcctggc actgcggaga agttgagccc caaggcggcc acgcttgccg 360 agcgcagccggcctggcctt cagcttgtac caggccatgg ccaaggacca ggcagtggag 420 aacatcctggtgtcacccgt ggtggtggcc tcgtcgctgg ggctcgtgtc gctgggcggc 480 aaggcgaccacggcgtcgca ggccaaggca gtgctgagcg ccgagcagct gcgcgacgag 540 gaggtgcacgccggcctggg cgagctgctg cgctcactca gcaactccac ggcgcgcaac 600 gtgacctggaagctgggcag ccgactgtac ggacccagct cagtgagctt cgctgatgac 660 ttcgtgcgcagcagcaagca gcactacaac tgcgagcact ccaagatcaa cttccgcgac 720 aagcgcagcgcgctgcagtc catcaacgag tgggccgcgc agaccaccga cggcaagctg 780 cccgaggtcaccaaggacgt ggagcgcacg gacggcgccc tgttagtcaa cgccatgttc 840 ttcaagccacactgggatga gaaattccac cacaagatgg tggacaaccg tggcttcatg 900 gtgactcggtcctataccgt gggtgtcatg atgatgcacc ggacaggcct ctacaactac 960 tacgacgacgagaaggaaaa gctgcaaatc gtggagatgc ccctggccca caagctctcc 1020 agcctcatcatcctcatgcc ccatcacgtg gagcctctcg agcgccttga aaagctgcta 1080 accaaagagcagctgaagat ctggatgggg aagatgcaga agaaggctgt tgccatctcc 1140 ttgcccaagggtgtggtgga ggtgacccat gacctgcaga aacacctggc tgggctgggc 1200 ctgactgaggccattgacaa gaacaaggcc gacttgtcac gcatgtcagg caagaaggac 1260 ctgtacctggccagcgtgtt ccacgccacc gcctttgagt tggacacaga tggcaaccct 1320 ttgaccagaattacgggcgg aggagtgcgc acccaagtgt tctacgccga ccaccccttc 1380 atttcctagtgcgggacacc caaagcggtc cctgctattc attgggcgcc tggtccggcc 1440 taagggtgacaagatgcgag acgagttata ggcctcaggg tgcacacagg atggcaggag 1500 gcatccaaaggctcctgaga cacatgggtg ctattggggt tgggggggag gtgaggtacc 1560 agccttggatactccatggg gtggggtgga aaagcagacc ggggttcccg tgtgcctgag 1620 cggacttcccagctagaatt cactccactt ggacatgggc cccagatacc atgatgctga 1680 gcccggaaactccacatcct gtgggacctg ggccatagtc attctgcctg ccctgaaagt 1740 cccagatcaagcctgcctca atcagtattc atatttatag ccaggtacct tctcacctgt 1800 gagaccaaattgagctaggg gggtcagcca gccctcttct gacactaaaa cacctcagct 1860 gcctccccagctctatccca acctctccca actataaaac taggtgctgc agcccctggg 1920 accaggcacccccagaatga cctggccgca gtgaggcgga ttgagaagga gctcccagga 1980 ggggcttctgggcagactct ggtcaagaag catcgtgtct ggcgttgtgg ggatgaactt 2040 tttgttttgtttcttccttt tttagttctt caaagatagg gagggaaggg ggaacatgag 2100 cctttgttgctatcaatcca agaacttatt tgtacatttt ttttttcaat aaaacttttc 2160 caatgacaaaaaaaaaaaaa aaaaaaa 2187 94 757 DNA Homo sapiens misc_feature (756) nequals a,t,g, or c 94 gacagtacgg tcggattccc gggtcgaccc acgcgtccgcggacggtgaa gaaggtgaag 60 atggcggtgg ccagggccgg ggtcttggga gtccagtggctgcaaagggc atcccggaac 120 gtgatgccgc tgggcgcacg gacagcctcc cacatgaccaaggacatgtt cccggggccc 180 tatcctagga ccccagaaga acgggccgcc gccgccaagaagtataatat gcgtgtggaa 240 gactacgaac cttacccgga tgatggcatg gggtatggcgactacccgaa gctccctgac 300 cgctcacagc atgagagaga tccatggtat agctgggaccagccgggcct gaggttgaac 360 tggggtgaac cgatgcactg gcacctagac atgtacaacaggaaccgtgt ggatacatcc 420 cccacacctg tttcttggca tgtcatgtgt atgcagctcttcggtttcct ggctttcatg 480 atattcatgt gctgggtggg ggacgtgtac cctgtctaccagcctgtggg accaaagcag 540 tatccttaca ataatctgta cctggaacga ggcggtgatccctccaaaga accagagcgg 600 gtggttcact atgagatctg aggaggcttc gtgggcttttgggtcctcta actaggactc 660 cctcattcct agaaatttaa ccttaatgaa atccctaataaaactcagtg ctgtgttaaa 720 aaaaaaaaaa aaaaaaaaaa aaaaaggggg gccccnn 75795 2394 DNA Homo sapiens misc_feature (1783) n equals a,t,g, or c 95ggcacgagca ctcctgcact tccccacccc cacgaccgaa cctggcttcg ctaacgccct 60cccagctccc tcgggcctga cttccggttt cctcgcgcgt ccctggcgcc gagccgcgga 120cagcagcccc ttttccggct gagagctcat ccacacttcc aatcactttc cggagtgctt 180cccctccctc cggcccgtgc tggtcccgac ggcgggcctg ggtctcgcgc gcgtattgct 240gggtaacggg ccttctcycg cgtcggcccg gcccctcctg cctcggctcg tccctccttc 300cagaacgtcc cgggctcctg ccgagtcaga agaaatggga ctccctccgc gacgtgcccg 360gagcagctcc cttcgctgtg gaagcggcgg tgtcttcgaa gaaaccggaa gcccgtggtg 420acccctggcg acccggtttg ttttcggtcc gtttccaaac actaaggaat cgaaactcgg 480cggccttggg ggcggcccta cgtagcctgg cttctggttg tcatggatgc actggtagaa 540gatgatatct gtattctgaa tcatgaaaaa gcccataaga gagatacagt gactccagtt 600tcaatatatt caggagatga atctgttgct tcccattttg ctcttgtcac tgcatatgaa 660gacatcaaaa aacgacttaa ggattcagag aaagagaact ctttgttaaa gaagagaata 720agatttttgg aagaaaagct aatagctcga tttgaagaag aaacaagttc cgtgggacga 780gaacaagtaa ataaggccta tcatgcatat cgagaggttt gcattgatag agataatttg 840aagagcaaac tggacaaaat gaataaagac aactctgaat ctttgaaagt attgaatgag 900cagctacaat ctaaagaagt agaactcctc cagctgagga cagaggtgga aactcagcag 960gtgatgagga atttaaatcc accttcatca aactgggagg tggaaaagtt gagctgtgac 1020ctgaagatcc atggtttgga acaagagctg gaactgatga ggaaagaatg tagcgatctc 1080aaaatagaac tacagaaagc caaacaaacg gatccatatc aggaagacaa tctgaagagc 1140agagatctcc aaaaactaag catttcaagt gataatatgc agcatgcata ctgggaactg 1200aagagagaaa tgtctaattt acatctggtg actcaagtac aagctgaact actaagaaaa 1260ctgaaaacct caactgcaat caagaaagcc tgtgcccctg taggatgcag tgaagacctt 1320ggaagagaca gcacaaaact gcacttgatg aattttactg caacatacac aagacatccc 1380cctctcttac caaatggcaa agctctttgt cataccacat cttccccttt accaggagat 1440gtaaaggttt tatcagagaa agcaatcctc caatcatgga cagacaatga gagatccatt 1500cctaatgatg gtacatgctt tcaggaacac agttcttatg gcagaaattc tctggaagac 1560aattcctggg tatttccaag tcctcctaaa tcaagtgaga cagcatttgg ggaaactaaa 1620actaaaactt tgcctttacc caaccttcca ccactgcatt acttggatca acataatcag 1680aactgccttt ataagaatta atttggaaga gattcacgat ttcaccatga ggacacttat 1740ctctttcagt ggtcctccca agaaattatt taacaaactg aanggagatt ttgattaaaa 1800ttttgcagag gtcttcagta tctatatttg aacacactgt acaatagtac aaaaaccaac 1860atagttggtt ttctagtatg aaagagcacc ctctagctcc atattctaag aatctgaaat 1920atgctactat actaattaat aagtaaactt aaggtgttta aaaaactctg ccttctatat 1980taattgtaaa attttgcctc tcagaagaat ggaattggag attgtagacg tggttttaca 2040aaatgtgaaa tgtctaaata tctgttcata aaaataaaag gaaaacatgt ttcttcaaat 2100tgcataatgg aacaaatggc aatgtgagta ggttacattt ctgttgttat aatgcgtaaa 2160gatattgaaa atataatgaa ataaaagcat cttaggttat accatcttta tatgctattg 2220cgtttcaata tttaagattt aaagtgattt tttggtcaca gtgttttgtt gataaaattt 2280ttttagaatt gaagtttgaa ttctaagact tgaaacaacc tgatcactga agccaacttt 2340gtcccagcac attccttaag tcctaattgg ggaaaaaaaa aaaaaaaaac tcga 2394 96 672DNA Homo sapiens 96 agtgctctgt tgcccaggct ggagtgcgtt agtgtaatgtcagtccactg caacctccac 60 ccccaggttc aagcaattct catgcctcag cctcccaagtagctgaaatt actggcatgc 120 accaccacac ccagctgatg tttatttatt tatttatatatttatttatt ttaggtgttt 180 tttttttttt tttttgagac ggagtcttgc tctgttgccctgggtgtggt tacgtggrat 240 taccatyctg ggtgactcac tgaaatgtac tcmcagtgagtcatgccttc maatgacatc 300 tcaagttctg cctgcttgga gatacatctg gggatcttaaggggtgaggg actactcaac 360 aagaaggaat ttagcctgtc tttttaaata aacggcatttctttttccta kaaaaatggg 420 aaattcttca attctctaat acagggacac tgagataacaaagaggaaag tgtctggttg 480 gaggttggga rgccaccctg gggtctctcc tacaaaaatggaaaagaaaa gaacggtgar 540 aaatcmagca aagcacaara aaktttccct ttgctaaaagggaaaagatg ccccmcaatg 600 cccataaaca tgaactgggg ataaggagga raatgtctctycttggcacc cccaaacaaa 660 cgttaattac cc 672 97 1419 DNA Homo sapiensmisc_feature (517) n equals a,t,g, or c 97 taagaacaga acagcaagtatgaaccacat ggaacttaaa acatatgggt gtgaagtcca 60 cttatgtaga caaaacttataatttccaaa ctgttgtcta gtatacagtg atcagttgct 120 ctctgttcaa gtcattccacacatttccct attttaggct attataatat agaaagaaaa 180 tgggaagcat tagttggagctagaaaatga actgtatatt attgctatat ttgctaatac 240 caactatttc aataagtgttgtaccatatg tagcattaaa tataaaatac ataaaagaat 300 gtacagaaaa tagcttttattgagtaatat tacatttcat ttatactgta gcaatatatt 360 tgtaggtata ctctgtaagggctttaaata aaagaggtcc attaatactt ccttataaaa 420 attctagtct gtttcattactgcccagatg ttttagagat aaatatttat gcagaaggta 480 ttttkgaaag tcyccytttgtctgatagag tttaacnaga tatttaaatt tagtgcycna 540 gaaatcccac aagtcacggtctaaacacac ttagaatact acagcataaa tctgttagca 600 ttanttgcca aataagacagttgggatccc aaaccccaag tccttgagca atgtttttcc 660 tcaaaaagct gctatnccaatgatatagga aaawacattg tgttttccta aacacacttt 720 tctttttaaa tgtgcttcattgtttgattt ggtcctgcct aaatttcaca agctaggcca 780 atgaaggctg aatcaaagacatttcatcca ccaatatcat gtgtagatat tatgtataga 840 aaataaaata aattatggctctaacttctg tgttgctgtt tatcttgtta tttttcggcg 900 ttatactaat gngtttattgagagcatttt accttccaga cttctcatgg ctaacttttg 960 gtctgwattt tgstccttagatgkgaatat ttcttattag tytgctycct gcwacgcaat 1020 gactgcattt ctatcatttctcagtttgtt agwatatgtg gatagtattc tactgtataa 1080 atgattgcaa agtttatcaaaaacaaatta ttatatgtag cttttctaca gtgctttgct 1140 aaaccatgta gtactagttaagtsttcctt gaaaataaag atacactctt ataggggaca 1200 gttcctgttc actcccaggaaactttttta aaagatgaca ctgaatgttt attgcacttt 1260 agtgcagtga agtggcaataaaacctaaca tgaatcaagg ttgtttatgg cagatgcatg 1320 tgttgcttta cagagtttagcaaaagctct taattttatg tcatactgta ttctactgaa 1380 taataaagct aacattattcaataataaaa tggaaaaaa 1419 98 1830 DNA Homo sapiens misc_feature (67) nequals a,t,g, or c 98 gcgaccgcgc ccttcagcta gctcgctcgc tcgctctgcttccctgctgc cggctgcgca 60 tggcttnggc gttggcggcg ctggcggcgg tcgagcngcctgcgsagccg gtaccagcag 120 ttgcagaatg aagaagagtc tggagaacct gaacaggctgcaggtgatgc tcctccacct 180 tacagcagca tttctgcaga gagcgcacat nattttgactacaaggatga gtctgggttt 240 ccaaagcccc catcttacaa tgtagctaca acactgcccagttatgatga agcggagagg 300 accaaggctg aagctactat ccctttggtt cctgggagagatgaggattt tgtgggtcgg 360 gatgattttg atgatgctga ccagctgagg ataggaaatgatgggatttt catgttaact 420 tttttcatgg cattcctctt taactggatt gggtttttcctgtctttttg cctgaccact 480 tcagctgcag gaaggtatgg ggccatttca ggatttggtctctctctaat taaatggatc 540 ctgattgtca ggttttccac ctatttccct ggatattttgatggtcagta ctggctctgg 600 tgggtgttcc ttgttttagg ctttctcctg tttctcagaggatttatcaa ttatgcaaaa 660 gttcggaaga tgccagaaac tttctcaaat ctccccaggaccagagttct ctttatttat 720 taaagatgtt ttctggcaaa ggccttcctg catttatgaattctctctca agaagcaaga 780 gaacacctgc aggaagtgaa tcaagatgca gaacacagaggaataatcac ctgctttaaa 840 aaaataaagt actgttgaaa agatcatttc tctctatttgttcctaggtg taaaatttta 900 atagttaatg cagaattctg taatcattga atcattagtggttaatgttt gaaaaagctc 960 ttgcaatcaa gtctgtgatg tattaataat gccttatatattgtttgtag tcattttaag 1020 tagcatgagc catgtccctg tagtcggtag ggggcagtcttgctttattc atcctccatc 1080 tcaaaatgaa cttggaatta aatattgtaa gatatgtataatgctggcca ttttaaaggg 1140 gttttctcaa aagttaaact tttgttatga ctgtgtttttgcacataatc catatttgct 1200 gttcaagtta atctagaaat ttattcaatt ctgtatgaacacctggaagc aaaatcatag 1260 tgcaaaaata catttaaggt gtggtcaaaa ataagtctttaattggtaaa taataagcat 1320 taatttttta tagcctgtat tcacaattct gcggtaccttattgtaccta agggattcta 1380 aaggtgttgt cactgtataa aacagaaagc actaggatacaaatgaagct taattactaa 1440 aatgtaattc ttgacactct ttctataatt agcgttcttcacccccaccc ccacccccac 1500 cccccttatt ttccttttgt ctcctggtga ttaggccaaagtctgggagt aaggagagga 1560 ttaggtactt aggagcaaag aaagaagtag cttggaacttttgagatgat ccctaacata 1620 ctgtactact tgcttttaca atgtgttagc agaaaccagtgggttataat gtagaatgat 1680 gtgctttctg cccaagtggt aattcatctt ggtttgctatgttaaaactg taaatacaac 1740 agaacattaa taaatatctc ttgtgtagca ccttttaaaaaaaaaaaaaa aaaaaaaaaa 1800 aaaaaaaaaa aancccgggg gggggccccn 1830 99 1145DNA Homo sapiens 99 tttttttttt tttttttttt ttgactgaac taagtggcttttttattaga gaaagccaga 60 attacaaaag acttcccttt tcttggggta tggctgtctcagcacaatac tcaacataac 120 tgcagaactg atgtggctca ggcaccctgg ttttaattccttgaggatct ggcaattggc 180 ttacgcaaaa ggtcaccatt tgaggtcctg ccttactaattatgtgctgc ccaacaacta 240 aatttgtaat ttgtttttct ctagtttgag cagggtctgaattttttcat ttatttcctt 300 ttttgccagc agacagactt gagtctgtaa agacaagcaaatacactgac agaagtttac 360 catagtttct aaaatgtaaa aaagaaaacc cccaaaagactcaagaaaat tagaccacaa 420 attttgcatt gttcattgta gcactattgg taataaaataacaaatgttt gtgcattttt 480 atgtgaagat ccttctcgta tttcatttgg aaagatgagcaagaggtctg cttccttcat 540 tttacttccc cttctgtttt tgaaaggcag tttcgccaagcttaatgcaa gaatatctga 600 ctgtttagaa gaaagatatt gccacaatct ctggatggttttccagggtt gtgttattac 660 tgagcttcat ctttccagaa tgagcaaaac actgtccagtctttgttacg attttgtaat 720 aaatgtgtac atttttttta aatttttgga catcacatgaataaaggtat gtatgtacga 780 atgtgtatat attatatata tgacatctat tttggaaaatgtttgccctg ctgtacctca 840 tttttaggag gtgtgcatgg atgcaatata tgaaaatgggacattctgga actgctggtc 900 aggggacttt gtcgccctgt gcactaaaag ggccagattttcagcagcca aggacatcca 960 tacccaagtg aatgtgatgg gacttaaaag aagtgaactgagacaattca ctctggctgt 1020 ttgaacagca gcgtttcata ggaagagaaa aaaagatcaatcttgtattt tctgaccaca 1080 taaaggcttc ttctctttgt aataaagtag aaaagctctcctcaaaaaaa aaaaaaaaaa 1140 aaaaa 1145 100 734 DNA Homo sapiens 100tacccggcgg attccaggaa ggtaaattta gtcctataat tttcagctta attataaaca 60aaggaacaaa taagtggaag ggcagctatt accattcgct tagtcaaaac attcggttac 120tgccctttaa tacactccta tcatcagcac ttccaccatg tattacaagt cttgacccat 180ccctgtcgta actccagtaa aagttactgt tactagaaaa tttttatcaa ttaactgaca 240aatagtttct ttttaaagta gtttcttcca tctttattct gactagcttc caaaatgtgt 300tccctttttg aatcgaggtt tttttgtttt gttttgtttt ctgaaaaaat catacaactt 360tgtgcttcta ttgctttttt gtgttttgtt aagcatgtcc cttggcccaa atggaagagg 420aaatgtttaa ttaatgcttt ttagtttaaa taaattgaat catttataat aatcagtgtt 480aacaatttag tgacccttgg taggttaaag gttgcattat ttatacttga gatttttttc 540ccctaactat tctgtttttt gtactttaaa actatggggg aaatatcact ggtctgtcaa 600gaaacagcag taattattac tgagttaaat tgaaaagtcc agtggaccag gcatttctta 660tataaataaa attggtggta ctaatgtgaa aaaaaaaaaa aaaaaaaact cgaggggggc 720ccggtaccct atta 734 101 713 DNA Homo sapiens misc_feature (27) n equalsa,t,g, or c 101 ccgcgggaac gctgtcctgg ctgccgncac ccgaacagcc tgtcctggtgccccggctcc 60 ctgccccgcg cccagtcatg accctgcgcc cctcactcct cccgctccatctgctgctgc 120 tgctgctgct cagtgcggcg gtgtgccggg ctgaggctgg gctcgaaaccgaaagtcccg 180 tccggaccct ccaagtggag accctggtgg agcccccaga accatgtgccgagcccgctg 240 cttttggaga cacgcttcac atacactaca cgggaagctt ggtagatggacgtattattg 300 acacctccct gaccagagac cctctggtta tagaacttgg ccaaaagcaggtgattccag 360 gtctggagca gagtcttctc gacatgtgtg tgggagagaa gcgaagggcaatcattcctt 420 ctcacttggc ctatggaaaa cggggatttc caccatctgt cccagcggatgcagtggtgc 480 agtatgacgt ggagctgatt gcactaatcc gagccaacta ctggctaaagctggtgaagg 540 gcattttgcc tctggtaggg atggccatgg tgccaccctc ctgggcctcattgggtatca 600 cctatacaga aaggccaata gacccaaagt ctccaaaaag aagctcaaggaagagaaacg 660 aaacaagagc aaaaagaaat aataaataat aaattttaaa aaacttaaaaaaa 713 102 1080 DNA Homo sapiens misc_feature (514) n equals a,t,g, orc 102 ccgatgtgga catcatcctg tctatcccca tgttcctgcg cctgtacctg atcgcccgag60 tcatgctgct gcacagaagc tcttcaccga tgcctcgtcc cgcagcatcg gggccctcaa 120caagatcaac ttcaacaccc gctttgtcat gaagacgctc atgaccatct gccctggcac 180tgtgctgctc gtgttcagca tctctctgtg gatcattgct gcctggaccg tccgtgtctg 240tgaaagtcct gaatcaccag cccagccttc tggctcatca cttcctgctt ggtaccatga 300ccagcaggac gtaactagta actttctggg tgccatgtgg ctcatctcca tcacattcct 360ttccattggt tatggggaca tggtgcccca cacatactgt gggaaaggtg tctgtctcct 420cactggcatc atgggtgcag gctgcactgc ccttgtggtg gccgtggtgg cccgaaagct 480ggaactcacc aaagcggaga agcacgttca taanttcatg atggacactc agctcaccaa 540gcggatcaag aatgytgcag ccaatgtcct tsgggaaaca tggttaatct ataaacacac 600aaagytgyta aagaagattg accatgccaa agtgaggaac accagaggaa gttcytccaa 660gtatccacca gttgaggagc gtcaagatgg aacagaggaa gctgagtgac caagccaaca 720ntctggtgga cctttccaag atgcagaatg tcmtgtatga cttaatcaca gaactcaatg 780accggagcga agacctggag aagcagattg gcagcctgga gtcgaagctg gagcatctca 840ccgccagctt caactccctg ccgctgctca tcgccgacac cctgcgccag cagcagcagc 900agctcctgtc tgccatcatc gaggcccggg gtgtcagcgt ggcagtgggc accacccaca 960ccccaatctc cgatagcccc attggggtca gctccacctc cttcccgacc ccgtacacaa 1020gttcaagcag ttgctaaata aatctcccca ctccagaagc attaaaaaaa aaaaaaaaaa 1080103 489 DNA Homo sapiens 103 ggcacgagag gctttgaagc atttttgtct gtgctccctgatcttcaggt caccaccatg 60 aagttcttag cagtcctggt actcttggga gtttccatctttctggtctc tgcccagaat 120 ccgacaacag ctgctccagc tgacacgtat ccagctactggtcctgctga tgatgaagcc 180 cctgatgctg aaaccactgc tgctgcaacc actgcgaccactgctgctcc taccactgca 240 accaccgctg cttctaccac tgctcgtaaa gacattccagttttacccaa atgggttggg 300 gatctcccga atggtagagt gtgtccctga gatggaatcagcttgagtct tctgcaattg 360 gtcacaacta ttcatgcttc ctgtgatttc atccaactacttaccttgcc tacgatatcc 420 cctttatctc taatcagttt attttctttc aaataaaaaataactatgag caacaaaaaa 480 aaaaaaaaa 489 104 1529 DNA Homo sapiensmisc_feature (7) n equals a,t,g, or c 104 gggcacnaga tggagctgccgtagcggacc cagcacagcc aggagcgtcc gggatgagct 60 cagccgcggc cgaccactgggcgtggttgc tggtgctcag cttcgtgttt ggatgcaatg 120 ttcttaggat cctcctcccgtccttctcat ccttcatgtc cagggtgctg cagaaggacg 180 cggacaggag tcacagatgagagcggagat ccaggacatg aagcaggagc tctccacagt 240 caacatgatg gacgagtttgccagatatgc caggctggaa agaaagatca acaagatgac 300 ggataagctc aaaacccatgtgaaagctcg gacagctcaa ttagccaaga taaaatgggt 360 gataagtgtc gctttctacgtattgcaggc tgccctgatg atctcactca tttggaagta 420 ttattctgtc cctgtggctgtcgtgccgag taaatggata acccctctag accgcctggt 480 agcctttcct actagagtagcaggtggtgt tggaattacc tgttggattt tagtctgtaa 540 caaagttgtc gctattgtgcttcatccgtt cagctgaaca ggaggatgga tacagccgcg 600 agtaaaaaaa cggatttcctcttcctagct taaaatctga tttacactgt tttgtttttt 660 aagaaacaaa agtgcatagtttagattttt tttttgttga atatgtttgt tcttggactt 720 tatgagatag tcttataagaatcacgattt tctacacctg tcattgagcc aagaaagtcc 780 agtttatgac acgtatgtactagtgaacac cgtcctcgat ctgtacgaaa tgtgaaatgt 840 ttagggacat ctccatgctgtcacttgtga tttgccctct tatgtatttt ggtcatattg 900 ccaactggaa agtcaaaattttctaacaac tttaagtaag ttctttgaag acttagtgct 960 gtttttaatc cagtttagaaagtaacttaa ttttaatacc rctactaaaa attcgaaaat 1020 ttcttcttta atcacattcaatatggttaa aagaacaaca ctaattgaca ttgcgtgggc 1080 tttttctccc tttgtttaaaatgtcatttg ttgagcaaga gttgtatagt attatctact 1140 tacttgaggc tgttaatttttcattacagt gttttgtaaa tgtatccacg agaccatgat 1200 gcattgtttt gtgctcaacttgtgttttgt atttaaagca ttttgaatga agtgtatttt 1260 ataagcattt aatatttatgctctttagaa tggaacacag aaaacaaacc ttataagtcc 1320 tgattaatct gaaccaataacctgtgtggc ctacaaagta taattctatt aaatgttcct 1380 taaaacactt ttttctaattaaaatctttg caaatgcttg tgtaacttcc tgccttacag 1440 ctacttgttt gctgtgagccacccgcaact gacaagtggc tgttaactga gtcaccatat 1500 cccagtaaag ctgaattttctcactaaaa 1529 105 2435 DNA Homo sapiens misc_feature (455) n equalsa,t,g, or c 105 atgaagggtc gttggtggga aagatggcgg cgactctggg accccttggtcgtggcagca 60 gtggcgrcga tgtttgtcgg ctcgggatgg gtccaggatg ttactccttcttcttttgtt 120 ggggtctggg caggggccac agcaagtcgg ggcgggtcaa acgttcgagtacttgaaacg 180 ggagcactcg ctgtcgaagc cctaccaggg tgtgggcaca ggcagttcctcactgtggaa 240 tctgatgggc aatgccatgg tgatgaccca gtatatccgc cttaccccagatatgcaaag 300 taaacagggt gccttgtgga accgggtgcc atgtttcctg agagactgggagttgcaggt 360 gcacttcaaa atccatggac aaggaaagaa gaatctgcat ggggatggcttggcaatctg 420 gtacacaaag grwtcggatg cagccagggc ctgtntttgg gaaacatggacaaatttgtg 480 gggctgggag tatttgtaga cacctacccc aatgaggaga agcagcaagagcgggtattc 540 ccctrcmtct cagccatggt gaacaacggc tccctcagct atgatcatgagcgggatggg 600 cggcctacag agctgggagg ctgcasagcc attgtccgca atcttcattacgacaccttc 660 ctggtgattc gctacgtcaa gaggcatttr acgataatga tggatattgatggcaagcat 720 gagtggaggg actgcattga agtgcccgga gtccgcctgc cccgcggctactacttcggc 780 acctcctcca tcactgggga tctctcagat aatcatgatg tcatttccttgaagttgttt 840 gaactgacag tggagagaac cccagaagag gaaaagctcc atcgagatgtgttcttgccc 900 tcagtggaca atatgaagct gcctgagatg acagctccac tgccgcccctgagtggcctg 960 gccctcttcc tcatcgtctt tttctccctg ggtgttttct gtatttgccatagtcattgg 1020 tatcatactc tacaacaaat ggcaggaaca gagccgaaag cgcttctactgagccctcct 1080 gctgccacca cttttgtgac tgtcacccat gaggtatgga aggagcaggcactggcctga 1140 gcatgcagcc tggagagtgt tcttgtctct agcagctggt tggggactatattctgtcac 1200 tggagttttg aatgcaggga ccccgcattc ccatggttgt gcatggggacatctaactct 1260 ggtctgggaa gccacccacc ccagggcaat gctgctgtga tgtgcctttccctgcagtcc 1320 ttccatgtgg gagcagaggt gtgaagagaa tttacgtggt tgtgatgccaaaatcacaga 1380 acagaatttc atagcccagg ctgccgtgtt gtttgactca gaaggcccttctacttcagt 1440 tttgaatcca caaagaatta aaaactggta acaccacagg ctttctgaccatccattcgt 1500 tgggttttgc atttgaccca accctctgcc tacctgagga gctttctttggaaaccagga 1560 tggaaacttc ttccctgcct taccttcctt tcactccatt cattgtcctctctgtgtgca 1620 acctgagctg ggaaaggcat ttggatgcct ctctgttggg gcctggggctgcagaacaca 1680 cctgcgtttc actggccttc attaggtggc cctagggaga tggctttctgctttggatca 1740 ctgttcccta gcatgggtct tgggtctatt ggcatgtcca tggccttcccaatcaagtct 1800 cttcaggccc tcagtgaagt ttggctaaag gttggtgtaa aaatcaagagaagcctggaa 1860 gacatcatgg atgccatgga ttagctgtgc aactgaccag ctccaggtttgatcaaacca 1920 aaagcaacat ttgtcatgtg gtctgaccat gtggagatgt ttctggacttgctagagcct 1980 gcttagctgc atgttttgta gttacgattt ttggaatccc actttgagtgctgaaagtgt 2040 aaggaagctt tcttcttaca ccttgggctt ggatattgcc cagagaagaaatttggcttt 2100 ttttttnctt aatggacaag agacagttgc tgttctcatg ttccaagtctgagagcaaca 2160 gaccctcatc atctgtgcct ggaagagttc actgtcattg agcagcacagcctgagtgct 2220 ggcctctgtc aacccttatt ccactgcctt atttgacaag gggttacatgctgctcacct 2280 tactgccctg ggattaaatc agttacaggc cagagtctcc ttggagggcctggaactctg 2340 agtcctccta tgaacctctg tagcctaaat gaaattctta aaatcaccgatggaaccaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaan 2435 106 805 DNAHomo sapiens 106 atgaaactta agaattgaat tggaaagact tctcaaagag aattgtatgtaacgatgttg 60 tattgatttt taagaaagta atttaatttg taaaacttct gctcgtttacactgcacatt 120 gaatacaggt aactaattgg aaggagaggg gaggtcactc ttttgatggtggccctgaac 180 ctcattctgg ttccctgctg cgctgcttgg tgtgacccac ggaggatccactcccaggat 240 gacgtgctcc gtagctctgc tgctgatact gggtctgcga tgcagcggcgtgaggcctgg 300 gctggttgga gaaggtcaca acccttctct gttggtctgc cttctgctgaaagactcgag 360 aaccaaccag ggaagctgtc ctggaggtcc ctggtcggag agggacatagaatctgtgac 420 ctctgacaac tgtgaagcca ccctgggcta cagaaaccac agtcttcccagcaattatta 480 caattcttga attccttggg gattttttac tgccctttca aagcacttaagtgttagatc 540 taacgtgttc cagtgtctgt ctgaggtgac ttaaaaaatc agaacaaaacttctattatc 600 cagagtcatg ggagagtaca ccctttccag gaataatgtt ttgggaaacactgaaatgaa 660 atcttcccag tattataaat tgtgtattta aaaaaaagaa acttttctgaatgcctactg 720 gcggtgtata ccaggcagtg tgccagttta aaaagatgaa aaagaataaaaacttttgag 780 gaacaaaaaa aaaaaaaaaa aaatt 805 107 1166 DNA Homo sapiensmisc_feature (1039) n equals a,t,g, or c 107 ggcacgagag gcgccagtcgcaggtgtgct gctgaggcgt gagaatggcg tcccgcggcc 60 ggcgtccgga gcatggcggacccccagagc tgttttatga cgagacagaa gcccggaaat 120 acgttcgcaa ctcacggatgattgatatcc agaccaggat ggctgggcga gcattggagc 180 ttctttatct gccagagaataagccctgtt acctgctgga tattggctgt ggcactgggc 240 tgagtggaag ttatctgtcagatgaagggc actattgggt gggcctggat atcagccctg 300 ccatgctgga tgaggctgtggaccgagaga tagagggaga cctgctgctg ggggatatgg 360 gccagggcat cccattcaagccaggcacat ttgatggttg catcagcatt tctgctgtgc 420 agtggctctg taatgctaacaagaagtctg aaaaccctgc caagcgcctg tactgctttt 480 ttgcttctct tttttctgttctcgtccggg gatcccgagc tgtcctgcag ctgtaccctg 540 agaactcaga gcagttggagctgatcacaa cccaggccac aaaggcaggc ttctccggtg 600 gcatggtggt agactaccctaacagtgcca aagcaaagaa attctacctc tgcttgtttt 660 ctgggccttc gacctttataccagaggggc tgagtgaaaa tcaggatgaa gttgaaccca 720 gggagtctgt gttcaccaatgagaggttcc cattaaggat gtcgaggcgg ggaatggtga 780 ggaagagtcg ggcatgggtgctggagaaga aggagcggca caggcgccag ggcagggaag 840 tcagacctga cacccagtacaccggccgca agcgcaagcc ccgcttctaa gtcaccacgc 900 ggttctggaa aggcacttgcctctgcactt ttctatattg ttcagctgac aaagtagtat 960 tttagaaaag ttctaaagttataaaaatgt tttctgcagt aaaaaaaaag ttctctgggc 1020 cgggcgtggt ggctcacanctgtaatccca gcaccttggg aggctgaggt gggaggatca 1080 tttgaggcca ggagtttgagacctgcctgg gcaacataat gaaacttcct ttccagggag 1140 aaaaaaaaaa aaaaaaaaaaactcga 1166 108 586 DNA Homo sapiens 108 agagcggacg aagctggataacaggggacc gatgatgtgg cgaccatcag ttctgctgct 60 tctgttgcta ctgaggcacggggcccaggg gaagccatcc ccagacgcag gccctcatgg 120 ccaggggagg gtgcaccaggcggcccccct gagcgacgct ccccatgatg acgcccacgg 180 gaacttccag tacgaccatgaggctttcct gggacgggaa gtggccaagg aattcgacca 240 actcacccca gaggaaagccaggcccgtct ggggcggatc gtggaccgca tggaccgcgc 300 gggggacggc gacggctgggtgtcgctggc cgagcttcgc gcgtggatcg cgcacacgca 360 gcagcggcac atacgggactcggtgagcgc ggcctgggac acgtacgaca cggaccgcga 420 cgggcgtgtg ggttgggaggagctgcgcaa cgycacctat ggccactasg sgcccgktga 480 agaatttcat gacgtggaggatgcagagac ytacaaaaag atgctggytc gggacgagcg 540 gcgtttccgg gtggccgaccaggatgggga ctcgatggcc actcga 586 109 1134 DNA Homo sapiens misc_feature(418) n equals a,t,g, or c 109 acccattgag cagaaggagg ccaggtgggaaagctcctgg gaagagcagc cagactggac 60 actgggctgc ttgagtcctg agtcacaattcagaattcct gggctccctg ggtgcattct 120 atcattccag ttgaaagttt gcttccttccagtcatgtgg ctcttcattc tactctcctt 180 ggctctcatt tcagatgcca tggtcatggatgaaaaggtc aagagaagtt tgtgctggac 240 acggcttctg ccatctgcaa ctacaatgcccaytacaaga atcaccccaa atactggtgc 300 cgaggytatt tccgtgayta ctgcaacatcatcgccttct cccctaacag caccaatcat 360 gtggccctga aggacacagg gaaccagctcattgtcacta tgtcctgcct gaacaaanaa 420 gacacgggct ggtactggtg tggcatccarcgggactttg cmagggatga catggatttt 480 acagagctga ttgtaactga cgacaaaggaaccctggcca atgacttttg gtctgggaaa 540 gacctatcag gcaacaaaac cagaagctgcaaggctccca aagttgtccg caagctgacc 600 gctccaggac gtccattctc atcatttgcatactgatcac gggtttggga atcatctctg 660 taatcagtca tttgaccaaa aggaggagaagtcaaaggaa tagaagggta ggcaacactt 720 tgaagccctt ctcgcgtgtc ctgactccaaaggaaatggc tcctactgaa cagatgtgac 780 tgaagwtttt tttaatttag ttncataaagtgatgnctac aacagawtaa tcacccatga 840 caactggccc cacacctcag agactgattctgatctccca ggaattctga aggaccctct 900 atccttgaca acaatcattt gcagccaggtagcaacggcr gtagtcagag gagctatgat 960 agaccacacc caagcaaggc tgccctcaaataacatctca agatcttagt tcttatgcat 1020 tccatcagtc agaagtgaag aagaggtggagaatctkgat tggggaccag gaaatcactt 1080 gtattttgtt agccaataaa ttcctagccagtgttgaatg aaaaaaaaaa aaaa 1134 110 1333 DNA Homo sapiens 110 cactttaaagctctgctgag ggagttcgga gcccaggctt tcaggcgacc tctgccctcc 60 ctgcctctcctcaccctccc tctcttcctg cagggcctgg gaagggcttt gagggagcct 120 gggagccatgtgaagagggg cacgcctggg ctgtcccaca gtttagatcc agttggaggt 180 tctccctggctcctgcaggc ctgcggggat ctctccccac ttcaggcctc cggcagctgc 240 ctgccctcttgtctgtgctt cagccctgca caaaagcagc ttggtgacac cactcagcca 300 cccagagtacgtgtttacag gctttccaga tcaccttcct gtggggtgaa cgtaatgagg 360 cggggctggtccttggaatt tcccctggaa aatggtaaca gactccatcc ttgacccggg 420 gatgagcatgaaggcattgt cccaaaggca gaggccaccg tggtaggaat tccaccaagg 480 ccagaagggaaaaaggaaga acccaccgtg tctggctgtg cgggccctgg ggagggtcgt 540 gagtgcagcccctctctact tcygtgcctt tgtaaaacgt gtagataacc gcagtggttg 600 gctgagccaagaactctcct aaatcagtgg ctttctcccc accccttgct ggggagtcat 660 ttttaaaaaaatctgtggga tataaaattg gcctcctgct gcttcagcct acctctccct 720 ctgctgacttaatgtcgtga ttctgtttct tcagatattt aaggctgtta ggttgtgtga 780 gccttgaagtgtgtgtgtgt gtcccagcga ctgtccactg tccaggagat gcatgtcttt 840 gtattggagatatttctgta actcattctc ttggtgctca cgattgccat ggccataggg 900 ccacagtgccgtatctgctg cagacatgat tgtttcttgt tctagaggtt ttcttgtttt 960 cgaatcttgcctgatgaatc cagccagacc aaggggccta gatttgacct ctgtcctggg 1020 ctcctgggccaggtgcagga acatctgagg ccactctgct ggccacctcc agtgggtgct 1080 gaccacaggatgggctttgt ttacactcat tttcaccctg attcttgccc ccactttcat 1140 aaaagaaacttcaaaatgct gacgctttgg agagtaagaa aatcaatctt ggctgggcac 1200 ggtggctcctgcctgtgatc ctagcacttt gggaggctga agctgaagga tcacttgagc 1260 tcaggagttggagaccaacc ctggcaacat aacaagaccc tgtctctaca aaaaaaaaaa 1320 aaaaaaaactcga 1333 111 1015 DNA Homo sapiens misc_feature (1014) n equals a,t,g,or c 111 ggcacgagcg gcacgagcgg cacgaggtga cttcaagtgt cggatcttttcagcctacat 60 caaggaggtg gaggaacggc cggcacccac cccgtgggct ccaagatgccctttggggaa 120 ctgatgttcg aatccagcag tagctgcggc tgggtacatg gcgtctgtttctcagccagc 180 gggagccgcg tggcctgggt aagccacgac agcaccgtct gcctggctgatgccgacaag 240 aagatggccg tcgcgactct ggcctctgaa acactaccac tgctggcgctgaccttcatc 300 acagacaaca gcctggtggc agcgggccac gactgcttcc cggtgctgttcacctatgac 360 gccgccgcgg ggatgctgag cttcggcggg cggctggacg ttcctaagcagagctcgcag 420 cgtggcttga cggcccgcga gcgcttccag aacctggaca agaaggcgagctccgagggt 480 ggcacggctg cgggcgcggg cctagactcg ctgcacaaga acagcgtcagccagatctcg 540 gtgctcagcg gcggcaaggc caagtgctcg cagttctgca ccactggcatggatggcggc 600 atgagtatct gggatgtgaa gagcttggag tcagccttga aggacctcaagatcaaatga 660 cctgtgagga atatgttgcc ttcatcctag ctgctgggga agcggggagaggggtcaggg 720 aggctaatgg ttgctttgct gaatgtttct ggggtaccaa tacgagttcccataggggct 780 gctccctcaa aaagggaggg gacagatggg gagcttttct tacctattcaaggaatacgt 840 gcctttttct taaatgcttt catttattga aaaaaaaaaa aaatgcccccaaagcactat 900 gctggtcatg aactgcttca aaatgtggag gtaataaaat gcaactgtgtaaaaaaaaaa 960 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaaaacnc 1015 112 711 DNA Homo sapiens misc_feature (345) n equals a,t,g,or c 112 ggcacgagcg aagaccctgt tcggaccctg ccccgattcc agactcaggtagatcgtcgg 60 cataccctct accgtggaca ccaggcagcc ctggggctga tggagagagatcaggtatcc 120 cccagggagt aggggctacc ttgaggggat gatagacctc ccccactcccagtgkkactc 180 tggaaatatg aaggaactag ggagtggaag agatttcaga gctggggagaggagttcctc 240 ccttcaaagc cagcaactgc ctttggggaa tgtcgggggg tctctcctttctcctgcttg 300 tttraggtgg tacacagtcc ccccttcamc tggsgggaag ctgtnccggacaractcatc 360 tcagctttcc cttggggcag gatcgggggc agcagctcca gcagaaacagcaggatctgg 420 agcaggaagg cctcgaggcc acacaggggc tgctggccgg cgagtgggccccacccctct 480 ggragctggg cagcctcttc caggccttcg tgaagaggga gagccaggcttatgcgtaag 540 cttcatagct tctgctggcc tggggtggac ccaggacccc tggggcctgggtgccctgag 600 tggtggtaaa gtggagcaat cccttcacgc tccttggcca tgttctgagcggccagcttg 660 gcctttgcct taataaatgt gctttatttt caaaaaaaaa aaaaaaaaac t711 113 1076 DNA Homo sapiens misc_feature (1029) n equals a,t,g, or c113 ggcacgaggg gaaagccatg ctcccaggac tccttccttg cagccttaaa tcggtctgta 60cggaaaattc cgcgccttag aaacccacgc ttgggtgtaa cttattattg ttcttcctga 120cctacttcct gtttatcact tccgggttca tcattttggc atttcggtga tcgggttgga 180actattgaag cccgctttca ggttcttttc cccattttcc ctttgaaagg aagacttctg 240gcttctccta aatctccgtt ctctgggtaa ggggagtcca agcctctgtc atgaggaacg 300gaaatgcgag ggcctcgggt gttactctaa aatccgccct cagcttgcac gccggaagct 360gcgattcctg cagcggaaga ggcgtgatct ggccttcgac tcgctatgtc cactaacaat 420atgtcggacc cacggaggcc gaacaaagtg ctgaggtaca agcccccgcc gagcgaatgt 480aacccggcct tggacgaccc gacgccggac tacatgaacc tgctgggcat gatcttcagc 540atgtgcggcc tcatgcttaa gctgaagtgg tgtgcttggg tcgctgtcta ctgctccttc 600atcagctttg ccaactctcg gagctcggag gacacgaagc aaatgatgag tagcttcatg 660ctgtccatct ctgccgtggt gatgtcctat ctgcagaatc ctcagcccat gacgccccca 720tggtgatacc agcctagaag ggtcacattt tggaccctgt ctatccacta ggcctgggct 780ttggctgcta aacctgctgc cttcagctgc catcctggac ttccctgaat gaggccgtct 840cggtgccccc agctggatag agggaacctg gccctttcct agggaacacc ctaggcttac 900ccctcctgcc tcccttcccc tgcctgctgc tgggggagat gctgtccatg tttctagggg 960tattcatttg ctttctcgtt gaaacctgtt gttaataaag tttttcactc tgaaaaaaaa 1020aaaaaaaana raaaacncgn gggggggccc ggaacccaat tcsccggata gtgagt 1076 1141525 DNA Homo sapiens misc_feature (78) n equals a,t,g, or c 114ccgctgctga taactatggc atcccccggg cctgcaggaa ttcggcacgg agctacggcg 60ccgcctggct cctgctgnca cctgcaggct cgtcgcgggt ggagcccacc caagacatca 120gcatcagcga ccagctgggg ggccaggacg tgcccgtgtt ccggaacctg tccctgctgg 180tggtgggtgt cggcgccgtg ttctcactgc tattccacct gggcacccgg gagaggcgcc 240ggccgcatgc ggasgagcca ggcgagcaca cccccctgtt ggcccctgcc acggcccagc 300ccctgctgct ctggaagcac tggctccggg agcsggcttt ctaccaggtg ggcatactgt 360acatgaccac caggctcatc gtgaacctgt cccagaccta catggccatg tacctcacct 420actcgctcca cctgcccaag aagttcatcg cgaccattcc cctggtgatg tacctcagcg 480gcttcttgtc ctccttcctc atgaagccca tcaacaagtg cattgggagg aacatgacct 540acttctcagg cctcctggtg atcctggcct ttgccgcctg ggtggcgctg gcggagggac 600tgggtgtggc cgtgtacgca gcggctgtgc tgctgggtgc tggctgtgcc accatcctcg 660tcacctcgct ggccatgacg gccgacctca tcggtcccca cacgaacagc ggactktcgt 720gtacggctcc atgagcttct tggataaggt ggccaatggg ctggcagtca tggccatcca 780gagcctgcac ccttgcccct cagagctctg ctgcagggcc tgcgtgagct tttaccactg 840ggcgatggtg gctgtgacgg gcggcgtggg cgtggccgct gccctgtgtc tctgtagcct 900cctgctgtgg ccgacccgcc tgcgacgctg ggaccgtgat gcccggccct gactcctgac 960agcctcctgc acctgtgcaa gggaactgtg gggacgcacg aggatgcccc ccarggcctt 1020ggggaaaagc ccccactgcc cctcactctt ctctggaccc ccaccctcca tcctcaccca 1080gctcccgggg gtggggtcgg gtgagggcag cagggatgcc cgccagggac ttgcaaggac 1140cccctgggtt ttgagggtgt cccattctca actctaatcc atcccagccc tctggaggat 1200ttggggtgcc cctctcggca gggaacagga agtaggaatc ccagaagggt ctgggggaac 1260cctaaccctg agctcagtcc agttcacccc tcacctccag cctgggggtc tccagacact 1320gccagggccc cctcaggacg gctggagcct ggaggagaca gccacggggt ggtgggctgg 1380gcctggaccc caccgtggtg ggcagcaggg ctgcccggca ggcttggtgg actctgctgg 1440cagcaaataa agagatgacg gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500aaaaaaaaaa aaacccaccg tccgc 1525 115 1350 DNA Homo sapiens misc_feature(15) n equals a,t,g, or c 115 ggcacgagtg cgcangcgtg gggctctctccttgtcagtc ggcgccgcgt gcgggctggt 60 ggctctgtgg cagcggcggc ggcaggactccggcactatg agcggcttca gcaccgagga 120 gcgcgccgcg ccttctccct ggagtaccgagtcttcctca aaaatgagaa aggacaatat 180 atatctccat ttcatgatat tccaatttatgcagataagg atgtgtttca catggtagtt 240 gaagtaccac gctggtctaa tgcaaaaatggagattgcta caaaggaccc tttaaaccct 300 attaaacaag atgtgaaaaa aggaaaacttcgctatgttg cgaatttgtt cccgtataaa 360 ggatatatct ggaactatgg tgccatccctcagacttggg aagacccagg gcacaatgat 420 aaacatactg gctgttgtgg tgacaatgacccaattgatg tgtgtgaaat tggaagcaag 480 gtatgtgcaa gaggtgaaat aattggcgtgaaagttctag gcatattggc tatgattgac 540 gaaggggaaa ccgactggaa agtcattgccattaatgtgg atgatcctga tgcagccaat 600 tataatgata tcaatgatgt caaacggctgaaacctggct acttagaagc tactgtggac 660 tggtttagaa ggtataaggt tcctgatggaaaaccagaaa atgagtttgc gtttaatgca 720 gaatttaaag ataaggactt tgccattgatattattaaaa gcactcatga ccattggaaa 780 gcattagtga ctaagaaaac gaatggaaaaggaatcagtt gcatgaatac aactttgtct 840 gagagcccct tcaagtgtga tcctgatgctgccagagcca ttgtggatgc tttaccacca 900 ccctgtgaat ctgcctgcac agtaccaacagacgtggata agtggttcca tcaccagaaa 960 aactaatgag atttctctgg aatacaagctgatattgcta catcgtgttc atctggatgt 1020 attagaagta aaagtagtag cttttcaaagctttaaattt gtagaactca tctaactaaa 1080 gtaaattctg ctgtgactaa tccaatatactcagaatgtt atccatctaa agcatttttc 1140 atatctcaac taagataact tttagcacatgcttaaatat caaagcagtt gtcatttgga 1200 agtcacttgt gaatagatgt gcaaggggagcacatattgg atgtatatgt taccatatgt 1260 taggaaataa aattattttg ctgaaaaaaaaaaaaaaaaa acctsggggg gggscccggt 1320 ccccatttgg ccctttgggg ggnggtttta1350 116 2527 DNA Homo sapiens 116 ctcttgctac cttcccggcg cagagaaccccggctgctca gcgcgctccg gggtcatgga 60 gatccccggg agcctgtgca agaaagtcaagctgagcaat aacgcgcaga actggggaat 120 gcagagagca accaatgtca cctaccaagcccatcatgtc agcaggaaca agagaggtca 180 ggtggtgggg accagaggtg gctttcgtggttgcacagtt tggctaacag gcttgtctgg 240 agcgggaaag actactgtga gcatggccttggaggagtac ctggtttgtc atggtattcc 300 atgctacact ctggatggtg acaatattcgtcaaggtctc aataaaaatc ttggctttag 360 tcctgaagac agagaagaga atgttcgacgcatcgcagaa gttgctaaac tgtttgcaga 420 tgctggctta gtgtgcatca caagtttcatatcaccttac actcaggatc gcaacaatgc 480 aaggcaaatt catgaaggtg caagtttaccgttttttgaa gtatttgttg atgctcctct 540 gcatgtttgt gaacagaggg atgtcaaaggactctacaaa aaagcccggg caggagaaat 600 taaaggtttc actgggatcg attctgaatatgaaaagcca gaggcccctg agttggtgct 660 gaaaacagac tcctgtgatg taaatgactgtgtccagcaa gttgtggaac ttctacagga 720 acgggatatt gtacctgtgg atgcatcttatgaagtaaaa gaactatatg tgccagaaaa 780 taaacttcat ttggcaaaaa cagatgcggaaacattacca gcactgaaaa ttaataaagt 840 ggatatgcag tgggtgcagg ttttggcagaaggttgggca accccattga atggctttat 900 gagagagagg gagtacttgc agtgccttcattttgattgt cttctggatg gaggtgtcat 960 taacttgtca gtacctatag ttctgactgcgactcatgaa gataaagaga ggctggacgg 1020 ctgtacagca tttgctctga tgtatgagggccgccgtgtg gccattcttc gcaatccaga 1080 gttttttgag cacaggaaag aggagcgctgtgccagacag tggggaacga catgcaagaa 1140 ccacccctat attaagatgg tgatggaacaaggagattgg ctgattggag gagatcttca 1200 agtcttggat cgagtttatt ggaatgatggtcttgatcag tatcgtctta ctcctactga 1260 gctaaagcag aaatttaaag atatgaatgctgatgctgtc tttgcatttc aactacgcaa 1320 cccagtgcac aatggacatg ccctgttaatgcaggatacc cataagcaac ttctagagag 1380 gggctaccgg cgccctgtcc tcctcctccaccctctgggt ggctggacaa aggatgacga 1440 tgttcctttg atgtggcgta tgaagcagcatgctgcagtg ttggaggaag gagttctgaa 1500 tcctgagacg acagtggtgg ccatcttcccatctcccatg atgtatgctg gaccaactga 1560 ggtccagtgg cattgcagag cacggatggttgcaggagcc aacttttaca ttgttggacg 1620 agaccctgct ggcatgcctc atccagaaacagggaaggat ctttatgagc caagtcatgg 1680 tgccaaagtg ctgacgatgg cccctggtttaatcactttg gaaatagttc cctttcgagt 1740 tgcagcttac aacaagaaaa agaagcgtatggactactat gactctgaac accatgaaga 1800 ctttgaattt atttcaggaa cacgaatgcgcaaacttgct cgagaaggcc agaaaccacc 1860 tgaaggtttc atggctccca aggcttggaccgtgctgaca gaatactaca aatccttgga 1920 gaaagcttag gctgttaacc cagtcactccacctttgaca cattactagt aacaagaggg 1980 gaccacatag tctctgttgg catttctttgtggtgtctgt ctggacatgc ttcctaaaaa 2040 cagaccattt tccttaactt gcatcagttttggtctgcct tatgagttct gttttgaaca 2100 agtgtaacac actgatggtt ttaatgtatcttttccactt attatagtta tattcctaca 2160 atacaatttt aaaattgtct ttttatattatatttatgct tctgtgtcat gattttttca 2220 agctgttata ttagttgtaa ccagtagtattcacattaaa tcttgctttt tttcccctta 2280 aaaaaagaaa aaaattacca aacaataaacttggctagac cttgttttga ggattttaca 2340 agacctttgt agcgattaga ttttttttctacattgaaaa tagaaactgc ttcctttctt 2400 ctttccagtc agctattggt ctttccagctgttataatct aaagtattct tatgatctgt 2460 gtaagctctg aatgaacttc tttactcaataaaattaatt ttttggcttc ttaaaaaaaa 2520 aaaaaaa 2527 117 1098 DNA Homosapiens misc_feature (88) n equals a,t,g, or c 117 cgcatcacag acaacccagaaggaaaatgg ttgggcagaa cagcaagggg ttcatatggc 60 tatattaaaa caactgctgtagagattnnc tatgattctt tgaaactgaa aaaagactct 120 cttggtgccc cttcaagacctattgaagat gaccaagaag tatatgatga tgttgcagag 180 caggatgata ttagcagccacagtcagagt ggaagtggag ggatattccc tccaccacca 240 gatgatgaca tttatgatgggattgaagag gaagatgctg atgatggttt ccctgctcct 300 cctaaacaat tggacatgggagatgaagtt tacgatgatg tggatacctc tgatttccct 360 gtttcatcag cagagatgagtcaaggaact aatgttggaa aagctaagac agaagaaaag 420 gaccttaaga agctaaaaaagcagraaaaa gaaraaaaag acttcaggaa aaaatttaaa 480 tatgatggtg aaattagagtcctatattca actaaagtta caacttccat aacttctaaa 540 aagtggggaa ccagagatctacaggtaaaa cctggtgaat ctctagaagt tatacaaacc 600 acagatgaca caaaagttctctgcagaaat gaagaaggga aatatggtta tgtccttcgg 660 agttacctag cggacaatgatggagagatc tatgatgata ttgctgatgg ctgcatctat 720 gacaatgact agcactcaactttggtcatt ctgctgtgtt cattaggtgc caatgtgaag 780 tctggatttt aattggcatgttattgggta tcmagaaaat taatgcacar aaccacttat 840 tatcatttgt tatgaaatcccaattatctt tacaaagtgt ttaaagtttg aacatagaaa 900 ataatctctc tgcttaattgttatctcaga agactacatt agtgagatgt aagaattatt 960 aaatattcca tttccgctttggctacaatt atgaagaagt tgaaggtact tcttttagac 1020 caccagtaaa taatcctccttcaaaaaata aaaataaaaa aaaaaaaaaa aaactcgagg 1080 gggggcccgg tacccaat1098 118 1679 DNA Homo sapiens misc_feature (1679) n equals a,t,g, or c118 tcgacccacg cgtccggcga gatccctacc gcagtagccg cctctgccgc cgcggagctt 60cccgaacctc ttcagccgcc cggagccgct cccggagccc ggccgtagag gctgcaatcg 120cagccgggag cccgcagccc gcgccccgag cccgccgccg cccttcgagg gcgccccagg 180ccgcgccatg gtgaaggtga cgttcaactc cgctctggcc cagaaggagg ccaagaagga 240cgagcccaag agcggcgagg aggcgctcat catccccccc gacgccgtcg cggtggactg 300caaggaccca gatgatgtgg taccagttgg ccaaagaaga gcctggtgtt ggtgcatgtg 360ctttggacta gcatttatgc ttgcaggtgt tattctagga ggagcatact tgtacaaata 420ttttgcactt caaccagatg acgtgtacta ctgtggaata aagtacatca aagatgatgt 480catcttaaat gagccctctg cagatgcccc agctgctctc taccagacaa ttgaagaaaa 540tattaaaatc tttgaagaag aagaagttga atttatcagt gtgcctgtcc cagagtttgc 600agatagtgat cctgccaaca ttgttcatga ctttaacaag aaacttacag cctatttaga 660tcttaacctg gataagtgct atgtgatccc tctgaacact tccattgtta tgccacccag 720aaacctactg gagttactta ttaacatcaa ggctggaacc tatttgcctc agtcctatct 780gattcatgag cacatggtta ttactgatcg cattgaaaac attgatcacc tgggtttctt 840tatttatcga ctgtgtcatg acaaggaaac ttacaaactg caacgcagag aaactattaa 900aggtattcag aaacgtgaag ccagcaattg tttcgcaatt cggcattttg aaaacaaatt 960tgccgtggaa actttaattt gttcttgaac agtcaagaaa aacattattg aggaaaatta 1020atatcacagc ataaccccac cctttacatt ttgtgcagtg attatttttt aaagtcttct 1080ttcatgtaag tagcaaacag ggctttacta tcttttcatc tcattaattc aattaaaacc 1140attaccttaa aatttttttc tttcgaagtg tggtgtcttt tatatttgaa ttagtaactg 1200tatgaagtca tagataatag tacatgtcac cttaggtagt aggaagaatt acaatttctt 1260taaatcattt atctggattt ttatgtttta ttagcatttt caagaagacg gattatctag 1320agaataatca tatatatgca tacgtaaaaa tggaccacag tgacttattt gtagttgtta 1380gttgccctgc tacctagttt gttagtgcat ttgagcacac attttaattt tcctctaatt 1440aaaatgtgca gtattttcag tgtcaaatat atttaactat ttagagaatg atttccacct 1500ttatgtttta atatcctagg catctgctgt aataatattt tagaaaatgt ttggaattta 1560agaaataact tgtgttacta atttgtataa cccatatctg tgcaatggaa tataaatatc 1620acaaagttgt ttaamwaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaan 1679119 1411 DNA Homo sapiens misc_feature (1391) n equals a,t,g, or c 119ggcacaggag cgacccggga gaaggagggc camgakgcgg aagcggagga gtctccagga 60gacccgggga cagcatcgcc caggcccctg tttgcaggcc tttcagatat atccatctca 120caagacatcc ccgtagaagg agaaatcacc attcctatga gatctcgcat ccgggagttt 180gacagctcca cattaaatga atctgttcgc aataccatca tgcgtgatct aaaagctgtt 240gggaaaaaat tcatgcatgt tttgtaccca aggaaaagta atactctttt gagagattgg 300gatttgtggg gccctttgat cctttgtgtg acactcgcat taatgctgca aagagactct 360gcagatagtg aaaaagatgg agggccccaa tttgcagagg tgtttgtcat tgtctggttt 420ggtgcagtta ccatcaccct caactcaaaa cttcttggag ggaacatatc tttttttcag 480agcctctgtg tgctgggtta ctgtatactt cccttgacag tagcaatgct gatttgccgg 540ctggtacttt tggctgatcc aggacctgta aacttcatgg ttcggctttt tgtggtgatt 600gtgatgtttg cctggtctat agttgcctcc acagctttcc ttgctgatag ccagcctcca 660aaccgcagag ccctagctgt ttatcctgtt ttcctgtttt actttgtcat cagttggatg 720attctcacct ttactcctca gtaaatcagg aatgggaaat taaaaaccag tgaattgaaa 780gcacatctga aagatgcaat tcaccatgga gctttgtctc tggcccttat ttgtctaatt 840ttggaggtat ttgataactg agtaggtgag gagattaaaa gggagccata tagcactgtc 900accccttatt tgaggaactg atgtttgaaa ggctgttctt ttctctctta atgtcatttc 960tttaaaaata catgtgcata ctacacacag tatataatgc ctccttaagg catgatggag 1020tcaccgtggt ccatttgggt gacaaccagt gacttgggaa gcacatagat acatcttaca 1080agttgaatag agttgataac tattttcagt tttgagaata ccagttcagg tgcagctctt 1140aaacacattg ccttatgact attagaatat gcctctcttt tcataaataa aaatacatgg 1200tctatatcca ttttctttta tttctctctc ttaagcttaa aaaggcaatg agagaggtta 1260ggagtgggtt catacacgga gaatgagaaa acatgcatta accaatattc agattttgat 1320caggggaaat tctayacttg ttgcaaaaaa aaaaaaaaaa aaactcgagg ggggcccggt 1380acccaatcgc ngtatatgat cgnaaacaat c 1411 120 2223 DNA Homo sapiensmisc_feature (338) n equals a,t,g, or c 120 cctccggaag cgtttccaactttccagaag tttctcggga cgggcaggag ggggtgggga 60 ctgccatata tagatcccgggagcagggga gcgggctaag agtagaatcg tgtcgcggct 120 cgagagcgag agtcacgtcccggcgctagc cagcccgacc caggcccacc gtggtgcacg 180 caaaccactt cctggccatgcgctccctcc tgcttctcag cgccttctgc ctcctggagg 240 cggccctggc cgccgaggtgaagaaacctg cagccgcagc agctcctggc actgcggaga 300 agttgagccc caaggcggccacgcttgccg agcgcagncg gcctggcctt cagcttgtac 360 caggccatgg ccaaggaccaggcagtggag aacatcctgg tgtcacccgt ggtggtggcc 420 tcgtcgctgg ggctcgtgtcgctgggcggc aaggcgacca cggcgtcgca ggccaaggca 480 gtgctgagcg ccgagcagctgcgcgacgag gaggtgcacg ccggcctggg cgagctgctg 540 cgctcactca gcaactcsacggcgcgcaac gtgacctgga agctgggcag ccgactgtac 600 ggacccagct cagtgagcttcgctgatgac ttcgtgcgca cagcaagcag cactacaact 660 gcgagcactc caagatcaacttccgcgaca agcgcacgcg ctgcagtcca tcaacgagtg 720 ggccgcgcag accaccgacggcaagctgcc cgaggtcacc aaggacgtgg agcgcacgga 780 cggcgccctg ytagtcaacgccatgttctt caagccacac tgggatgaga aattccacca 840 caagatggtg gacaaccgtggcttcatggt gactcggtcc tatacygtgg gtgtcatgat 900 gatgcaccgg acaggcctctacaactacta cgacgacgag aaggaaaagc tgcaaatcgt 960 ggagatgccc ctggcccacaagctctccag cctcatcatc ctcatgcccc atcacgtgga 1020 gcctctcgag cgccttgaaaagctgctaac caaagagcag ctgaagatct ggatggggaa 1080 gatgcagaag aaggctgttgccatctcctt gcccaagggt gtggtggagg tgacccatga 1140 cctgcagaaa cacctggctgggctgggcct gactgaggcc attgacaaga acaaggccga 1200 cttrtcacgc atgtcaggcaagaaggacct gtacctggcc agcgtgttcc acgccaccgc 1260 ctttgagttg gacacagatggcaacccctt tgaccaggac atctacgggc gcgaggagct 1320 gcgcasccca agctgttctacgccgaccac cccttcatct tcctagtgcg ggacacccaa 1380 agcggctccc tgctattcattgggcgcctg gtccggccta agggtgacaa gatgcgagac 1440 gagttatagg gcctcagggtgcacacagga tggcaggagg catccaaagg ctcctgagac 1500 acatgggtgc tattggggttgggggggagg tgaggtacca gccttggata ctccatgggg 1560 tgggggtgga aaarcagaccggggttcccg tgtgcctgag cggaccttcc cagctagaat 1620 tcactccact tggacatgggccccagatac catgatgctg agcccggaaa ctccacatcc 1680 tgtgggacct gggccatagtcattctgcct gccctgaaag tcccagatca agcctgcctc 1740 aatcagtatt catatttatagccaggtacc ttctcacctg tgagaccaaa ttgagctagg 1800 ggggtcagcc agccctcttctgacactaaa acacctcagc tgcctcccca gctctatccc 1860 aacctctccc aactataaaactaggtgctg cagcccctgg gaccaggcac ccccagaatg 1920 acctggccgc agtgaggcggattgagaagg agctcccagg aggggcttct gggcagactc 1980 tggtcaagaa gcatcgtgtctggcgttgtg gggatgaact ttttgttttg tttcttcctt 2040 ttttagttct tcaaagatagggagggaagg gggaacatga gcctttgttg ctatcaatcc 2100 aagaacttat ttgtacattttttttttcaa taaaactttt ccaatgacaa aaaaaaaaaa 2160 aaaaaaaaaa mwmggggsgggccgctccta gagggatccc tccganggng cccaatcgaa 2220 aat 2223 121 31 PRTHomo sapiens 121 Met Lys Lys Gln Ser Lys Arg Cys Leu Trp Lys Pro Pro GlySer Leu 1 5 10 15 Arg Arg Leu Trp Trp Met Arg Ala Leu Leu Ile Leu LysTyr Ile 20 25 30 122 198 PRT Homo sapiens MISC_FEATURE (29) Xaa equalsany of the L-amino acids commonly found in naturally occurring proteins122 Met Lys Lys Ser Leu Glu Asn Leu Asn Arg Leu Gln Val Met Leu Leu 1 510 15 His Leu Thr Ala Ala Phe Leu Gln Arg Ala Gln His Xaa Phe Asp Tyr 2025 30 Lys Asp Glu Ser Gly Phe Pro Lys Pro Pro Ser Tyr Asn Val Ala Thr 3540 45 Thr Leu Pro Ser Tyr Asp Glu Ala Glu Arg Thr Lys Ala Glu Ala Thr 5055 60 Ile Pro Leu Val Pro Gly Arg Asp Glu Asp Phe Val Gly Arg Asp Asp 6570 75 80 Phe Asp Asp Ala Asp Gln Leu Arg Ile Gly Asn Asp Gly Ile Phe Met85 90 95 Leu Thr Phe Phe Met Ala Phe Leu Phe Asn Trp Ile Gly Phe Phe Leu100 105 110 Ser Phe Cys Leu Thr Thr Ser Ala Ala Gly Arg Tyr Gly Ala IleSer 115 120 125 Gly Phe Gly Leu Ser Leu Ile Lys Trp Ile Leu Ile Val ArgPhe Ser 130 135 140 Thr Tyr Phe Pro Gly Tyr Phe Asp Gly Gln Tyr Trp LeuTrp Trp Val 145 150 155 160 Phe Leu Val Leu Gly Phe Leu Leu Phe Leu ArgGly Phe Ile Asn Tyr 165 170 175 Ala Lys Val Arg Lys Met Pro Glu Thr PheSer Asn Leu Pro Arg Thr 180 185 190 Arg Val Leu Phe Ile Tyr 195 123 39PRT Homo sapiens 123 Met His Asn Gln Arg Gln Val Phe Leu Phe His Leu PheSer Asn Tyr 1 5 10 15 Leu Leu Ser Ile Asn Ser Val Pro Gly Thr Leu LeuAla Ala Thr Tyr 20 25 30 Cys Leu Asn Met Thr Tyr Gly 35 124 23 PRT Homosapiens 124 Met Arg Lys Lys Phe Leu Leu Ala Gln Val Phe Leu Ser Leu SerVal 1 5 10 15 Met Pro Ser Met Pro Val Thr 20 125 110 PRT Homo sapiens125 Met Val Leu Leu Cys Leu Leu Leu Val Pro Leu Leu Leu Ser Leu Phe 1 510 15 Val Leu Gly Leu Phe Leu Trp Phe Leu Lys Arg Glu Arg Gln Glu Glu 2025 30 Tyr Ile Glu Glu Lys Lys Arg Val Asp Ile Cys Arg Glu Thr Pro Asn 3540 45 Ile Cys Pro His Ser Gly Glu Asn Thr Glu Tyr Asp Thr Ile Pro His 5055 60 Thr Asn Arg Thr Ile Leu Lys Glu Asp Pro Ala Asn Thr Val Tyr Ser 6570 75 80 Thr Val Glu Ile Pro Lys Lys Met Glu Asn Pro His Ser Leu Leu Thr85 90 95 Met Pro Asp Thr Pro Arg Leu Phe Ala Tyr Glu Asn Val Ile 100 105110 126 63 PRT Homo sapiens 126 Met Leu Leu Leu Phe Ile Tyr Phe Tyr SerHis Pro Ala Pro Val Pro 1 5 10 15 Ala Gly Ala Thr Ser Lys Pro Arg TyrArg Val Ile Thr Cys Gly Pro 20 25 30 Ala Ser Val Phe Ser Thr Ser Phe SerHis Ser Pro Pro Ala Arg Cys 35 40 45 Leu Gly Arg Leu Glu Gln Met Phe HisPhe Gly Leu Ala Ser Gly 50 55 60 127 30 PRT Homo sapiens 127 Met Pro PhePro Ile Ser Ile Leu Gln Leu Cys Leu Gln Ile Ser Asn 1 5 10 15 Leu SerPhe Cys Leu Gln Lys Ile Tyr Lys Ile Pro Phe Val 20 25 30 128 53 PRT Homosapiens 128 Met Ala Ala Ala Cys Arg Ser Val Lys Gly Leu Val Ala Val IleThr 1 5 10 15 Gly Gly Ala Ser Gly Leu Gly Leu Ala Thr Ala Asp Asp LeuTrp Gly 20 25 30 Arg Glu Pro Leu Leu Cys Phe Trp Thr Cys Pro Thr Arg ValGly Arg 35 40 45 Pro Lys Pro Arg Ser 50 129 57 PRT Homo sapiensMISC_FEATURE (10) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 129 Met Leu Leu Val Tyr Asp Leu Tyr Leu XaaPro Lys Leu Trp Ala Leu 1 5 10 15 Ala Thr Pro Gln Lys Asn Gly Lys GlyAla Arg Xaa Gly Asp Gly Thr 20 25 30 Pro Ala Gln Ala Phe Trp Asp Phe TrpSer His Leu Ile Ser Ala Asp 35 40 45 Pro Gln Thr Trp Glu Arg Ala Ala Pro50 55 130 216 PRT Homo sapiens 130 Met Arg Leu Ser Ala Leu Leu Ala LeuAla Ser Lys Val Thr Leu Pro 1 5 10 15 Pro His Tyr Arg Tyr Gly Met SerPro Pro Gly Ser Val Ala Asp Lys 20 25 30 Arg Lys Asn Pro Pro Trp Ile ArgArg Arg Pro Val Val Val Glu Pro 35 40 45 Ile Ser Asp Glu Asp Trp Tyr LeuPhe Cys Gly Asp Thr Val Glu Ile 50 55 60 Leu Glu Gly Lys Asp Ala Gly LysGln Gly Lys Val Val Gln Val Ile 65 70 75 80 Arg Gln Arg Asn Trp Val ValVal Gly Gly Leu Asn Thr His Tyr Arg 85 90 95 Tyr Ile Gly Lys Thr Met AspTyr Arg Gly Thr Met Ile Pro Ser Glu 100 105 110 Ala Pro Leu Leu His ArgGln Val Lys Leu Val Asp Pro Met Asp Arg 115 120 125 Lys Pro Thr Glu IleGlu Trp Arg Phe Thr Glu Ala Gly Glu Arg Val 130 135 140 Arg Val Ser ThrArg Ser Gly Arg Ile Ile Pro Lys Pro Glu Phe Pro 145 150 155 160 Arg AlaAsp Gly Ile Val Pro Glu Thr Trp Ile Asp Gly Pro Lys Asp 165 170 175 ThrSer Val Glu Asp Ala Leu Glu Arg Thr Tyr Val Pro Cys Leu Lys 180 185 190Thr Leu Gln Glu Glu Val Met Glu Ala Met Gly Ile Lys Glu Thr Arg 195 200205 Lys Tyr Lys Lys Val Tyr Trp Tyr 210 215 131 49 PRT Homo sapiens 131Met Ser Leu Arg Gln Lys Ser Ser Phe Arg Leu Met Val Met Ser Leu 1 5 1015 Thr Ile Leu Lys Leu Ser Lys Thr Thr Val Leu Cys Leu Arg Cys Leu 20 2530 His Ser Leu Lys Leu Thr Trp Arg Asp Gly Ala Arg Cys Ile Asn Ala 35 4045 Glu 132 68 PRT Homo sapiens 132 Met Ser Gly Ser Phe Ile Leu Cys LeuAla Leu Val Thr Arg Trp Ser 1 5 10 15 Pro Gln Ala Ser Ser Val Pro LeuAla Val Tyr Glu Ser Lys Thr Arg 20 25 30 Lys Ser Tyr Arg Ser Gln Arg AspArg Asp Gly Lys Asp Arg Ser Gln 35 40 45 Gly Met Gly Leu Ser Leu Leu ValGlu Thr Arg Lys Leu Leu Leu Ser 50 55 60 Ala Asn Gln Gly 65 133 52 PRTHomo sapiens 133 Met Cys Phe Arg Phe Phe Leu Phe Cys Ser Arg Ile Leu LeuLys Leu 1 5 10 15 Phe Phe Leu Leu Phe Pro Ala Ser Ala Phe Pro Leu SerThr Arg Ser 20 25 30 Ser Leu Ser Val Asn Glu His Val Val Val Ser Pro ArgSer Thr Val 35 40 45 Ser Ile Ser Arg 50 134 540 PRT Homo sapiensMISC_FEATURE (137) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 134 Met Val Arg Thr Asp Gly His Thr Leu SerGlu Lys Arg Asn Tyr Gln 1 5 10 15 Val Thr Asn Ser Met Phe Gly Ala SerArg Lys Lys Phe Val Glu Gly 20 25 30 Val Asp Ser Asp Tyr His Asp Glu AsnMet Tyr Tyr Ser Gln Ser Ser 35 40 45 Met Phe Pro His Arg Ser Glu Lys AspMet Leu Ala Ser Pro Ser Thr 50 55 60 Ser Gly Gln Leu Ser Gln Phe Gly AlaSer Leu Tyr Gly Gln Gln Ser 65 70 75 80 Ala Leu Gly Leu Pro Met Arg GlyMet Ser Asn Asn Thr Pro Gln Leu 85 90 95 Asn Arg Ser Leu Ser Gln Gly ThrGln Leu Pro Ser His Val Thr Pro 100 105 110 Thr Thr Gly Val Pro Thr MetSer Leu His Thr Pro Pro Ser Pro Ser 115 120 125 Arg Gly Ile Leu Pro MetAsn Pro Xaa Asn Met Met Asn His Ser Gln 130 135 140 Val Gly Gln Gly IleGly Ile Pro Ser Arg Thr Asn Ser Met Ser Ser 145 150 155 160 Ser Gly LeuGly Ser Pro Asn Arg Ser Ser Pro Ser Ile Ile Cys Met 165 170 175 Pro LysGln Gln Pro Ser Arg Gln Pro Phe Thr Val Asn Ser Met Ser 180 185 190 GlyPhe Gly Met Asn Arg Asn Gln Ala Phe Gly Met Asn Asn Ser Leu 195 200 205Ser Ser Asn Ile Phe Asn Gly Thr Asp Gly Ser Glu Asn Val Thr Gly 210 215220 Leu Asp Leu Ser Asp Phe Pro Ala Leu Ala Asp Arg Asn Arg Arg Glu 225230 235 240 Gly Ser Gly Asn Pro Thr Pro Leu Ile Asn Pro Leu Ala Gly ArgAla 245 250 255 Pro Tyr Val Gly Met Val Thr Lys Pro Ala Asn Glu Gln SerGln Asp 260 265 270 Phe Ser Ile His Asn Glu Asp Phe Pro Ala Leu Pro GlySer Ser Tyr 275 280 285 Lys Asp Pro Thr Ser Ser Asn Asp Asp Ser Lys SerAsn Leu Asn Thr 290 295 300 Ser Gly Lys Thr Thr Ser Ser Thr Asp Gly ProLys Phe Pro Gly Asp 305 310 315 320 Lys Ser Ser Thr Thr Gln Asn Asn AsnGln Gln Lys Lys Gly Ile Gln 325 330 335 Val Leu Pro Asp Gly Arg Val ThrAsn Ile Pro Gln Gly Met Val Thr 340 345 350 Asp Gln Phe Gly Met Ile GlyLeu Leu Thr Phe Ile Arg Ala Ala Glu 355 360 365 Thr Asp Pro Gly Met ValHis Leu Ala Leu Gly Ser Asp Leu Thr Thr 370 375 380 Leu Gly Leu Asn LeuAsn Ser Pro Glu Asn Leu Tyr Pro Lys Phe Ala 385 390 395 400 Ser Pro TrpAla Ser Ser Pro Cys Arg Pro Gln Asp Ile Asp Phe His 405 410 415 Val ProSer Glu Tyr Leu Thr Asn Ile His Ile Arg Asp Lys Leu Ala 420 425 430 AlaIle Lys Leu Gly Arg Tyr Gly Glu Asp Leu Leu Phe Tyr Leu Tyr 435 440 445Tyr Met Asn Gly Gly Asp Val Leu Gln Leu Leu Ala Ala Val Glu Leu 450 455460 Phe Asn Arg Asp Trp Arg Tyr His Lys Glu Glu Arg Val Trp Ile Thr 465470 475 480 Arg Ala Pro Gly Met Glu Pro Thr Met Lys Thr Asn Thr Tyr GluArg 485 490 495 Gly Thr Tyr Tyr Phe Phe Asp Cys Leu Asn Trp Arg Lys ValAla Lys 500 505 510 Glu Phe His Leu Glu Tyr Asp Lys Leu Glu Glu Arg ProHis Leu Pro 515 520 525 Ser Thr Phe Asn Tyr Asn Pro Ala Gln Gln Ala Phe530 535 540 135 57 PRT Homo sapiens 135 Met Ile Cys Pro Gln Cys Pro LeuSer Leu Leu Cys Leu Ile Ser Ser 1 5 10 15 Leu Cys Ser Leu Val Ile GlnIle Ser Leu Lys Thr Ile Arg Asp Ile 20 25 30 Thr Leu Leu Asn Met Val GlyIle Lys Phe Ser Ile Ser Leu Ser Asn 35 40 45 Lys Ile Asn Ile Asn Ser ArgThr Trp 50 55 136 201 PRT Homo sapiens 136 Met Thr Leu Arg Pro Ser LeuLeu Pro Leu His Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Ser Ala Ala ValCys Arg Ala Glu Ala Gly Leu Glu Thr Glu 20 25 30 Ser Pro Val Arg Thr LeuGln Val Glu Thr Leu Val Glu Pro Pro Glu 35 40 45 Pro Cys Ala Glu Pro AlaAla Phe Gly Asp Thr Leu His Ile His Tyr 50 55 60 Thr Gly Ser Leu Val AspGly Arg Ile Ile Asp Thr Ser Leu Thr Arg 65 70 75 80 Asp Pro Leu Val IleGlu Leu Gly Gln Lys Gln Val Ile Pro Gly Leu 85 90 95 Glu Gln Ser Leu LeuAsp Met Cys Val Gly Glu Lys Arg Arg Ala Ile 100 105 110 Ile Pro Ser HisLeu Ala Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val 115 120 125 Pro Ala AspAla Val Val Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile 130 135 140 Arg AlaAsn Tyr Trp Leu Lys Leu Val Lys Gly Ile Leu Pro Leu Val 145 150 155 160Gly Met Ala Met Val Pro Ala Leu Leu Gly Leu Ile Gly Tyr His Leu 165 170175 Tyr Arg Lys Ala Asn Arg Pro Lys Val Ser Lys Lys Lys Leu Lys Glu 180185 190 Glu Lys Arg Asn Lys Ser Lys Lys Lys 195 200 137 216 PRT Homosapiens 137 Met Phe Leu Arg Leu Tyr Leu Ile Ala Arg Val Met Leu Leu HisSer 1 5 10 15 Lys Leu Phe Thr Asp Ala Ser Ser Arg Ser Ile Gly Ala LeuAsn Lys 20 25 30 Ile Asn Phe Asn Thr Arg Phe Val Met Lys Thr Leu Met ThrIle Cys 35 40 45 Pro Gly Thr Val Leu Leu Val Phe Ser Ile Ser Leu Trp IleIle Ala 50 55 60 Ala Trp Thr Val Arg Val Cys Glu Ser Pro Glu Ser Pro AlaGln Pro 65 70 75 80 Ser Gly Ser Ser Leu Pro Ala Trp Tyr His Asp Gln GlnAsp Val Thr 85 90 95 Ser Asn Phe Leu Gly Ala Met Trp Leu Ile Ser Ile ThrPhe Leu Ser 100 105 110 Ile Gly Tyr Gly Asp Met Val Pro His Thr Tyr CysGly Lys Gly Val 115 120 125 Cys Leu Leu Thr Gly Ile Met Gly Ala Gly CysThr Ala Leu Val Val 130 135 140 Ala Val Val Ala Arg Lys Leu Glu Leu ThrLys Ala Glu Lys His Val 145 150 155 160 His Asn Phe Met Met Asp Thr GlnLeu Thr Lys Arg Ile Lys Asn Ala 165 170 175 Ala Ala Asn Val Leu Arg GluThr Trp Leu Ile Tyr Lys His Thr Lys 180 185 190 Leu Leu Lys Lys Ile AspHis Ala Lys Val Arg Lys His Gln Arg Lys 195 200 205 Phe Leu Pro Ser TyrPro Pro Val 210 215 138 102 PRT Homo sapiens 138 Met Ser Asn Thr Thr ValPro Asn Ala Pro Gln Ala Asn Ser Asp Ser 1 5 10 15 Met Val Gly Tyr ValLeu Gly Pro Phe Phe Leu Ile Thr Leu Val Gly 20 25 30 Val Val Val Ala ValVal Met Tyr Val Gln Lys Lys Lys Arg Val Asp 35 40 45 Arg Leu Arg His HisLeu Leu Pro Met Tyr Ser Tyr Asp Pro Ala Glu 50 55 60 Glu Leu His Glu AlaGlu Gln Glu Leu Leu Ser Asp Met Gly Asp Pro 65 70 75 80 Lys Val Val HisGly Trp Gln Ser Gly Tyr Gln His Lys Arg Met Pro 85 90 95 Leu Leu Asp ValLys Thr 100 139 112 PRT Homo sapiens 139 Met Arg Glu Cys Gln Glu Glu SerPhe Trp Lys Arg Ala Leu Pro Phe 1 5 10 15 Ser Leu Val Ser Met Leu ValThr Gln Gly Leu Val Tyr Gln Gly Tyr 20 25 30 Leu Ala Ala Asn Ser Arg PheGly Ser Leu Pro Lys Val Ala Leu Ala 35 40 45 Gly Leu Leu Gly Phe Gly LeuGly Lys Val Ser Tyr Ile Gly Val Cys 50 55 60 Gln Ser Lys Phe His Phe PheGlu Asp Gln Leu Arg Gly Ala Gly Phe 65 70 75 80 Gly Pro Gln His Asn ArgHis Cys Leu Leu Thr Cys Glu Glu Cys Lys 85 90 95 Ile Lys His Gly Leu SerGlu Lys Gly Asp Ser Gln Pro Ser Ala Ser 100 105 110 140 20 PRT Homosapiens 140 Met Lys Asn Asp Arg Asn Gln Gly Phe Ser Leu Leu Gln Leu IleAsp 1 5 10 15 Trp Asn Lys Pro 20 141 30 PRT Homo sapiens 141 Met Gly ThrGln Pro Pro Val Val Ala Gly Phe Thr Ile Pro Met Leu 1 5 10 15 Gly TyrThr Val Arg Val Leu Thr Phe His Leu Ser Cys Ser 20 25 30 142 99 PRT Homosapiens 142 Met Lys Ile Pro Val Leu Pro Ala Val Val Leu Leu Ser Leu LeuVal 1 5 10 15 Leu His Ser Ala Gln Gly Ala Thr Leu Gly Gly Pro Glu GluGlu Ser 20 25 30 Thr Ile Glu Asn Tyr Ala Ser Arg Pro Glu Ala Phe Asn ThrPro Phe 35 40 45 Leu Asn Ile Asp Lys Leu Arg Ser Ala Phe Lys Ala Asp GluPhe Leu 50 55 60 Asn Trp His Ala Leu Phe Glu Ser Ile Lys Arg Lys Leu ProPhe Leu 65 70 75 80 Asn Trp Asp Ala Phe Pro Lys Leu Lys Gly Leu Arg SerAla Thr Pro 85 90 95 Asp Ala Gln 143 8 PRT Homo sapiens 143 Met Val TrpGly Leu Leu Leu Gly 1 5 144 39 PRT Homo sapiens MISC_FEATURE (30) Xaaequals any of the L-amino acids commonly found in naturally occurringproteins 144 Met Leu Pro Leu Leu Ser Leu Leu Phe Leu Phe Phe Ser Thr ValSer 1 5 10 15 Ser Phe Cys Gly Met Pro Leu Arg Ala His Thr Arg Ala XaaAla His 20 25 30 Thr Arg Thr Phe Ala Ser Arg 35 145 131 PRT Homo sapiens145 Met Ile Cys Glu Thr Lys Ala Arg Lys Ser Ser Gly Gln Pro Gly Arg 1 510 15 Leu Pro Pro Pro Thr Leu Ala Pro Pro Gln Pro Pro Leu Pro Glu Thr 2025 30 Ile Glu Arg Pro Val Gly Thr Gly Ala Met Val Ala Arg Ser Ser Asp 3540 45 Leu Pro Tyr Leu Ile Val Gly Val Val Leu Gly Ser Ile Val Leu Ile 5055 60 Ile Val Thr Phe Ile Pro Phe Cys Leu Trp Arg Ala Trp Ser Lys Gln 6570 75 80 Lys His Thr Thr Asp Leu Gly Phe Pro Arg Ser Ala Leu Pro Pro Ser85 90 95 Cys Pro Tyr Thr Met Val Pro Leu Gly Gly Leu Pro Gly His Gln Ala100 105 110 Val Asp Ser Pro Thr Ser Val Ala Ser Val Asp Gly Pro Val LeuMet 115 120 125 Gly Ser Thr 130 146 32 PRT Homo sapiens 146 Met Gly AlaPro Ser Leu Thr Met Leu Leu Leu Leu Lys Val Gln Pro 1 5 10 15 Arg ArgThr Gln Ala Phe Asp Ala His Trp Val Gly Leu Pro Leu Leu 20 25 30 147 14PRT Homo sapiens 147 Met Cys Leu Ile Phe Leu Leu Leu Leu Leu Leu Ser PheSer 1 5 10 148 8 PRT Homo sapiens 148 His Pro His Gln Asp Ser Gln Pro 15 149 68 PRT Homo sapiens 149 Met Asn Thr Ser Tyr Ile Leu Arg Leu ThrVal Val Val Ser Val Val 1 5 10 15 Ile Tyr Leu Ala Ile His Pro Leu LeuSer Phe Ser Leu Glu Ser Pro 20 25 30 Leu Leu Val Pro Trp Arg Asp Cys CysGln Asn Ile Trp Lys Ser Gly 35 40 45 Ser Val Trp Tyr Lys Arg Trp Thr LeuPro His Met Glu Val Cys Cys 50 55 60 Gln Asp Leu His 65 150 26 PRT Homosapiens 150 Met Leu Lys Ile Phe Lys Glu Trp Glu Asn Leu Asn Leu Ile LeuThr 1 5 10 15 Ser Ile Arg Ile Leu Glu Arg Gln Asn Met 20 25 151 195 PRTHomo sapiens 151 Met Asp Cys Glu Val Asn Asn Gly Ser Ser Leu Arg Asp GluCys Ile 1 5 10 15 Thr Asn Leu Leu Val Phe Gly Phe Leu Gln Ser Cys SerAsp Asn Ser 20 25 30 Phe Arg Arg Glu Leu Asp Ala Leu Gly His Glu Leu ProVal Leu Ala 35 40 45 Pro Gln Trp Glu Gly Tyr Asp Glu Leu Gln Thr Asp GlyAsn Arg Ser 50 55 60 Ser His Ser Arg Leu Gly Arg Ile Glu Ala Asp Ser GluSer Gln Glu 65 70 75 80 Asp Ile Ile Arg Asn Ile Ala Arg His Leu Ala GlnVal Gly Asp Ser 85 90 95 Met Asp Arg Ser Ile Pro Pro Gly Leu Val Asn GlyLeu Ala Leu Gln 100 105 110 Leu Arg Asn Thr Ser Arg Ser Glu Glu Asp ArgAsn Arg Asp Leu Ala 115 120 125 Thr Ala Leu Glu Gln Leu Leu Gln Ala TyrPro Arg Asp Met Glu Lys 130 135 140 Glu Lys Thr Met Leu Val Leu Ala LeuLeu Leu Ala Lys Lys Val Ala 145 150 155 160 Ser His Thr Pro Ser Leu LeuArg Asp Val Phe His Thr Thr Val Asn 165 170 175 Phe Ile Asn Gln Asn LeuArg Thr Tyr Val Arg Ser Leu Ala Arg Asn 180 185 190 Gly Met Asp 195 15291 PRT Homo sapiens MISC_FEATURE (85) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 152 Met Ser Leu SerLeu Val Ser Val Ser Val Gly Pro Ser Thr Leu Ala 1 5 10 15 Cys Ser PheLeu Arg Pro Lys Ala Arg Pro Ser Lys Arg Ser Pro Arg 20 25 30 Asn Tyr ThrAsp Ser Thr Ser Pro Gly Gly Pro Arg Ala Pro Arg Gly 35 40 45 Gly Ala TrpArg Leu Ser Ser Gln Gln Asn Ser Ser Pro Lys Gly Val 50 55 60 Ala Val AlaLys Ala Ser Tyr Arg Pro Val Leu Cys Phe Leu Pro Gly 65 70 75 80 Pro TrpSer Ser Xaa Pro Xaa Ala Phe Leu Ile 85 90 153 31 PRT Homo sapiens 153Met Gly Thr Leu Ser Ala Glu Cys Ser Gly Pro Ala Thr Leu Gly Leu 1 5 1015 Cys Leu Val Val Pro Trp Asn Ser Ser Gly Leu Ser Gln Pro Pro 20 25 30154 90 PRT Homo sapiens 154 Met Lys Phe Leu Ala Val Leu Val Leu Leu GlyVal Ser Ile Phe Leu 1 5 10 15 Val Ser Ala Gln Asn Pro Thr Thr Ala AlaPro Ala Asp Thr Tyr Pro 20 25 30 Ala Thr Gly Pro Ala Asp Asp Glu Ala ProAsp Ala Glu Thr Thr Ala 35 40 45 Ala Ala Thr Thr Ala Thr Thr Ala Ala ProThr Thr Ala Thr Thr Ala 50 55 60 Ala Ser Thr Thr Ala Arg Lys Asp Ile ProVal Leu Pro Lys Trp Val 65 70 75 80 Gly Asp Leu Pro Asn Gly Arg Val CysPro 85 90 155 89 PRT Homo sapiens 155 Met Ile Ile Ser Leu Phe Ile TyrIle Phe Leu Thr Cys Ser Asn Thr 1 5 10 15 Ser Pro Ser Tyr Gln Gly ThrGln Leu Gly Leu Gly Leu Pro Ser Ala 20 25 30 Gln Trp Trp Pro Leu Thr GlyArg Arg Met Gln Cys Cys Arg Leu Phe 35 40 45 Cys Phe Leu Leu Gln Asn CysLeu Phe Pro Phe Pro Leu His Leu Ile 50 55 60 Gln His Asp Pro Cys Glu LeuVal Leu Thr Ile Ser Trp Asp Trp Ala 65 70 75 80 Glu Ala Gly Ala Ser LeuTyr Ser Pro 85 156 174 PRT Homo sapiens 156 Met Ser Ser Ala Ala Ala AspHis Trp Ala Trp Leu Leu Val Leu Ser 1 5 10 15 Phe Val Phe Gly Cys AsnVal Leu Arg Ile Leu Leu Pro Ser Phe Ser 20 25 30 Ser Phe Met Ser Arg ValLeu Gln Lys Asp Ala Glu Gln Glu Ser Gln 35 40 45 Met Arg Ala Glu Ile GlnAsp Met Lys Gln Glu Leu Ser Thr Val Asn 50 55 60 Met Met Asp Glu Phe AlaArg Tyr Ala Arg Leu Glu Arg Lys Ile Asn 65 70 75 80 Lys Met Thr Asp LysLeu Lys Thr His Val Lys Ala Arg Thr Ala Gln 85 90 95 Leu Ala Lys Ile LysTrp Val Ile Ser Val Ala Phe Tyr Val Leu Gln 100 105 110 Ala Ala Leu MetIle Ser Leu Ile Trp Lys Tyr Tyr Ser Val Pro Val 115 120 125 Ala Val ValPro Ser Lys Trp Ile Thr Pro Leu Asp Arg Leu Val Ala 130 135 140 Phe ProThr Arg Val Ala Gly Gly Val Gly Ile Thr Cys Trp Ile Leu 145 150 155 160Val Cys Asn Lys Val Val Ala Ile Val Leu His Pro Phe Ser 165 170 157 45PRT Homo sapiens 157 Met Gly Lys Leu Ile Asn Ile Val Ile Arg Lys Pro LeuLeu Leu Leu 1 5 10 15 Leu Val Gln Cys Glu Asn Cys Cys Arg Lys Asn MetLeu Tyr Asn Ile 20 25 30 Phe Leu Asn Ile His Asn Ile His Lys Phe Ser AsnHis 35 40 45 158 23 PRT Homo sapiens 158 Met Val Ala Ser Thr Leu Val ThrAsn Leu Phe Gly Val Ala Phe Ala 1 5 10 15 Thr Thr Ala Ala Thr Arg Ala 20159 70 PRT Homo sapiens MISC_FEATURE (33) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 159 Met Leu Met AlaPro Val Val Cys Leu Ser Phe Ser Pro Cys Pro Ala 1 5 10 15 Asp Thr SerLeu Thr Gly Asp Gly Leu Lys Ala Gly Leu Glu Arg Gly 20 25 30 Xaa Ala LeuVal Thr Leu Phe Asp Ser Val Thr His Phe Leu Ala His 35 40 45 Thr Leu PheGlu Leu Leu Asp Phe Gln Leu Ala Phe Leu Arg Ser Gly 50 55 60 Lys Gln ThrAla Pro His 65 70 160 323 PRT Homo sapiens 160 Met Leu Leu Leu Leu LeuLeu Leu Gly Ser Gly Gln Gly Pro Gln Gln 1 5 10 15 Val Gly Ala Gly GlnThr Phe Glu Tyr Leu Lys Arg Glu His Ser Leu 20 25 30 Ser Lys Pro Tyr GlnGly Val Gly Thr Gly Ser Ser Ser Leu Trp Asn 35 40 45 Leu Met Gly Asn AlaMet Val Met Thr Gln Tyr Ile Arg Leu Thr Pro 50 55 60 Asp Met Gln Ser LysGln Gly Ala Leu Trp Asn Arg Val Pro Cys Phe 65 70 75 80 Leu Arg Asp TrpGlu Leu Gln Val His Phe Lys Ile His Gly Gln Gly 85 90 95 Lys Lys Asn LeuHis Gly Asp Gly Leu Ala Ile Trp Tyr Thr Arg Asn 100 105 110 Arg Met GlnPro Gly Pro Val Phe Gly Asn Met Asp Lys Phe Val Gly 115 120 125 Leu GlyVal Phe Val Asp Thr Tyr Pro Asn Glu Glu Lys Gln Gln Glu 130 135 140 ArgVal Phe Pro Tyr Ile Ser Ala Met Val Asn Asn Gly Ser Leu Ser 145 150 155160 Tyr Asp His Glu Arg Asp Gly Arg Pro Thr Glu Leu Gly Gly Cys Thr 165170 175 Ala Ile Val Arg Asn Leu His Tyr Asp Thr Phe Leu Val Ile Arg Tyr180 185 190 Val Lys Arg His Leu Thr Ile Met Met Asp Ile Asp Gly Lys HisGlu 195 200 205 Trp Arg Asp Cys Ile Glu Val Pro Gly Val Arg Leu Pro ArgGly Tyr 210 215 220 Tyr Phe Gly Thr Ser Ser Ile Thr Gly Asp Leu Ser AspAsn His Asp 225 230 235 240 Val Ile Ser Leu Lys Leu Phe Glu Leu Thr ValGlu Arg Thr Pro Glu 245 250 255 Glu Glu Lys Leu His Arg Asp Val Phe LeuPro Ser Val Asp Asn Met 260 265 270 Lys Leu Pro Glu Met Thr Ala Pro LeuPro Pro Leu Ser Gly Leu Ala 275 280 285 Leu Phe Leu Ile Val Phe Phe SerLeu Val Phe Ser Val Phe Ala Ile 290 295 300 Val Ile Gly Ile Ile Leu TyrAsn Lys Trp Gln Glu Gln Ser Arg Lys 305 310 315 320 Arg Phe Tyr 161 320PRT Homo sapiens MISC_FEATURE (120) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 161 Met Pro Ser Glu TyrThr Tyr Val Lys Leu Arg Ser Asp Cys Ser Arg 1 5 10 15 Pro Ser Leu GlnTrp Tyr Thr Arg Ala Gln Ser Lys Met Arg Arg Pro 20 25 30 Ser Leu Leu LeuLys Asp Ile Leu Lys Cys Thr Leu Leu Val Phe Gly 35 40 45 Val Trp Ile LeuTyr Ile Leu Lys Leu Asn Tyr Thr Thr Glu Glu Cys 50 55 60 Asp Met Lys LysMet His Tyr Val Asp Pro Asp His Val Lys Arg Ala 65 70 75 80 Gln Lys TyrAla Gln Gln Val Leu Gln Lys Glu Cys Arg Pro Lys Phe 85 90 95 Ala Lys ThrSer Met Ala Leu Leu Phe Glu His Arg Tyr Ser Val Asp 100 105 110 Leu LeuPro Phe Val Gln Lys Xaa Pro Lys Asp Ser Glu Ala Glu Ser 115 120 125 LysTyr Asp Pro Pro Phe Gly Phe Arg Lys Phe Ser Ser Lys Val Gln 130 135 140Thr Leu Leu Glu Leu Leu Pro Glu His Asp Leu Pro Glu His Leu Lys 145 150155 160 Ala Lys Thr Cys Arg Arg Cys Val Val Ile Gly Ser Gly Gly Ile Leu165 170 175 His Gly Leu Glu Leu Gly His Thr Leu Asn Gln Phe Asp Val ValIle 180 185 190 Arg Leu Asn Ser Ala Pro Val Glu Gly Tyr Ser Glu His ValGly Asn 195 200 205 Lys Thr Thr Ile Arg Met Thr Tyr Pro Glu Gly Ala ProLeu Ser Asp 210 215 220 Leu Glu Tyr Tyr Ser Asn Asp Leu Phe Val Ala ValLeu Phe Lys Ser 225 230 235 240 Val Asp Phe Asn Trp Leu Gln Ala Met ValLys Lys Glu Thr Leu Pro 245 250 255 Phe Trp Val Arg Leu Phe Phe Trp LysGln Val Ala Glu Lys Ile Pro 260 265 270 Leu Gln Pro Lys His Phe Arg IleLeu Asn Pro Val Ile Ile Lys Glu 275 280 285 Thr Ala Phe Xaa His Pro SerVal Leu Arg Ala Ser Val Lys Val Leu 290 295 300 Gly Ala Glu Ile Arg ThrSer Pro Gln Ser Val Ser Leu Pro Leu Ser 305 310 315 320 162 31 PRT Homosapiens 162 Met Thr Leu Asp Val Gln Thr Val Val Val Phe Ala Val Ile ValVal 1 5 10 15 Leu Leu Leu Val Asn Val Ile Leu Met Phe Phe Leu Gly ThrArg 20 25 30 163 72 PRT Homo sapiens MISC_FEATURE (26) Xaa equals any ofthe L-amino acids commonly found in naturally occurring proteins 163 MetLeu Pro Leu Leu Phe Cys Ala Phe Cys Leu His Lys Leu Gly Pro 1 5 10 15Leu Leu Phe Leu Tyr Asp Val Leu Met Xaa His Glu Ala Val Met Arg 20 25 30Thr His Gln Ile Gln Leu Pro Asp Pro Glu Phe Pro Ser Gln Gln Asn 35 40 45Gln Val Leu Asn Lys Thr Leu Phe Asn Lys Leu Lys Lys Lys Lys Lys 50 55 60Lys Lys Lys Xaa Xaa Xaa Lys Lys 65 70 164 281 PRT Homo sapiens 164 MetAla Ser Arg Gly Arg Arg Pro Glu His Gly Gly Pro Pro Glu Leu 1 5 10 15Phe Tyr Asp Glu Thr Glu Ala Arg Lys Tyr Val Arg Asn Ser Arg Met 20 25 30Ile Asp Ile Gln Thr Arg Met Ala Gly Arg Ala Leu Glu Leu Leu Tyr 35 40 45Leu Pro Glu Asn Lys Pro Cys Tyr Leu Leu Asp Ile Gly Cys Gly Thr 50 55 60Gly Leu Ser Gly Ser Tyr Leu Ser Asp Glu Gly His Tyr Trp Val Gly 65 70 7580 Leu Asp Ile Ser Pro Ala Met Leu Asp Glu Ala Val Asp Arg Glu Ile 85 9095 Glu Gly Asp Leu Leu Leu Gly Asp Met Gly Gln Gly Ile Pro Phe Lys 100105 110 Pro Gly Thr Phe Asp Gly Cys Ile Ser Ile Ser Ala Val Gln Trp Leu115 120 125 Cys Asn Ala Asn Lys Lys Ser Glu Asn Pro Ala Lys Arg Leu TyrCys 130 135 140 Phe Phe Ala Ser Leu Phe Ser Val Leu Val Arg Gly Ser ArgAla Val 145 150 155 160 Leu Gln Leu Tyr Pro Glu Asn Ser Glu Gln Leu GluLeu Ile Thr Thr 165 170 175 Gln Ala Thr Lys Ala Gly Phe Ser Gly Gly MetVal Val Asp Tyr Pro 180 185 190 Asn Ser Ala Lys Ala Lys Lys Phe Tyr LeuCys Leu Phe Ser Gly Pro 195 200 205 Ser Thr Phe Ile Pro Glu Gly Leu SerGlu Asn Gln Asp Glu Val Glu 210 215 220 Pro Arg Glu Ser Val Phe Thr AsnGlu Arg Phe Pro Leu Arg Met Ser 225 230 235 240 Arg Arg Gly Met Val ArgLys Ser Arg Ala Trp Val Leu Glu Lys Lys 245 250 255 Glu Arg His Arg ArgGln Gly Arg Glu Val Arg Pro Asp Thr Gln Tyr 260 265 270 Thr Gly Arg LysArg Lys Pro Arg Phe 275 280 165 81 PRT Homo sapiens 165 Met Glu Lys IlePro Glu Val Thr Asn Ser Asn Ser Ser Phe His Ala 1 5 10 15 His Asp LeuGly Phe Cys Val Leu Ser Ile Ala Thr Ser Lys Ser Arg 20 25 30 Lys Ala ProAla Pro His Ala Gln Lys Cys Asn Leu Lys Ser Leu Arg 35 40 45 Ser Ser AlaGln Thr Asp Ile Asn Lys Pro Val Phe Ser Leu His Pro 50 55 60 Glu Pro ProGly Lys Ser Gly Ala Gln Thr Gln Ser Lys Ala Pro Phe 65 70 75 80 Leu 166327 PRT Homo sapiens MISC_FEATURE (300) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 166 Met Trp Arg ProSer Val Leu Leu Leu Leu Leu Leu Leu Arg His Gly 1 5 10 15 Ala Gln GlyLys Pro Ser Pro Asp Ala Gly Pro His Gly Gln Gly Arg 20 25 30 Val His GlnAla Ala Pro Leu Ser Asp Ala Pro His Asp Asp Ala His 35 40 45 Gly Asn PheGln Tyr Asp His Glu Ala Phe Leu Gly Arg Glu Val Ala 50 55 60 Lys Glu PheAsp Gln Leu Thr Pro Glu Glu Ser Gln Ala Arg Leu Gly 65 70 75 80 Arg IleVal Asp Arg Met Asp Arg Ala Gly Asp Gly Asp Gly Trp Val 85 90 95 Ser LeuAla Glu Leu Arg Ala Trp Ile Ala His Thr Gln Gln Arg His 100 105 110 IleArg Asp Ser Val Ser Ala Ala Trp Asp Thr Tyr Asp Thr Asp Arg 115 120 125Asp Gly Arg Val Gly Trp Glu Glu Leu Arg Asn Ala Thr Tyr Gly His 130 135140 Tyr Ala Pro Gly Glu Glu Phe His Asp Val Glu Asp Ala Glu Thr Tyr 145150 155 160 Lys Lys Met Leu Ala Arg Asp Glu Arg Arg Phe Arg Val Ala AspGln 165 170 175 Asp Gly Asp Ser Met Ala Thr Arg Glu Glu Leu Thr Ala PheLeu His 180 185 190 Pro Glu Glu Phe Pro His Met Arg Asp Ile Val Ile AlaGlu Thr Leu 195 200 205 Glu Asp Leu Asp Arg Asn Lys Asp Gly Tyr Val GlnVal Glu Glu Tyr 210 215 220 Ile Ala Asp Leu Tyr Ser Ala Glu Pro Gly GluGlu Glu Pro Ala Trp 225 230 235 240 Val Gln Thr Glu Arg Gln Gln Phe ArgAsp Phe Arg Asp Leu Asn Lys 245 250 255 Asp Gly His Leu Asp Gly Ser GluVal Gly His Trp Val Leu Pro Pro 260 265 270 Ala Gln Asp Gln Pro Leu ValGlu Ala Asn His Leu Leu His Glu Ser 275 280 285 Asp Thr Asp Lys Asp GlyArg Leu Ser Lys Ala Xaa Ile Leu Gly Asn 290 295 300 Trp Asn Met Phe ValGly Ser Gln Ala Thr Asn Tyr Gly Glu Asp Leu 305 310 315 320 Thr Arg HisHis Asp Glu Leu 325 167 65 PRT Homo sapiens 167 Met Ile Lys Ile Leu LysGlu Ala Ile Glu Glu Thr Ser Phe Cys Ser 1 5 10 15 Phe Trp Arg Ile SerPhe Gln Leu Ser Ile His His Ile Phe Leu Ile 20 25 30 Phe Cys Ala Gln LeuThr Thr Leu Leu Tyr Ser Thr Phe Leu Phe Ile 35 40 45 Pro Ile Ser Trp PheLeu Ile Val Pro Gly Ala Val Asp Lys Thr Ile 50 55 60 Leu 65 168 159 PRTHomo sapiens 168 Met Trp Leu Phe Ile Leu Leu Ser Leu Ala Leu Ile Ser AspAla Met 1 5 10 15 Val Met Asp Glu Lys Val Lys Arg Ser Phe Val Leu AspThr Ala Ser 20 25 30 Ala Ile Cys Asn Tyr Asn Ala His Tyr Lys Asn His ProLys Tyr Trp 35 40 45 Cys Arg Gly Tyr Phe Arg Asp Tyr Cys Asn Ile Ile AlaPhe Ser Pro 50 55 60 Asn Ser Thr Asn His Val Ala Leu Lys Asp Thr Gly AsnGln Leu Ile 65 70 75 80 Val Thr Met Ser Cys Leu Asn Lys Glu Asp Thr GlyTrp Tyr Trp Cys 85 90 95 Gly Ile Gln Arg Asp Phe Ala Arg Asp Asp Met AspPhe Thr Glu Leu 100 105 110 Ile Val Thr Asp Asp Lys Gly Thr Trp Pro MetThr Leu Val Trp Glu 115 120 125 Arg Leu Ser Gly Thr Lys Pro Glu Ala AlaArg Leu Pro Lys Leu Ser 130 135 140 Ala Arg Leu Thr Ala Pro Gly Arg ProPhe Ser Ser Phe Ala Tyr 145 150 155 169 123 PRT Homo sapiensMISC_FEATURE (3) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 169 Met Ala Xaa His Phe Leu Leu Val Ala LeuGln Ser Val Pro His Cys 1 5 10 15 Pro His Leu Leu Glu Glu Glu His LysLeu Cys Lys Val Ser His Phe 20 25 30 Ser Gly Val Thr Leu Val Thr Ser ArgGln Asp Ser Ser Ser Tyr Val 35 40 45 Pro Val Gln Thr Leu Phe Ile His LeuGly Pro Trp Ala Trp Asp Leu 50 55 60 Xaa Pro Cys Thr Ala Glu Asp Pro GluAla Glu Arg Ser Leu Arg Leu 65 70 75 80 Cys His Ser His Leu Ala Arg XaaAsn Val Ser Pro Ser Gln Ala Ala 85 90 95 Glu Gly Xaa Xaa Xaa Arg Gly CysGln His Arg Gly Ser Arg Glu Leu 100 105 110 Thr Phe Leu Ser Ala Glu AsnGlu Ala Gly Ile 115 120 170 129 PRT Homo sapiens 170 Met Lys Val Gly AlaArg Ile Arg Val Lys Met Ser Val Asn Lys Ala 1 5 10 15 His Pro Val ValSer Thr His Trp Arg Trp Pro Ala Glu Trp Pro Gln 20 25 30 Met Phe Leu HisLeu Ala Gln Glu Pro Arg Thr Glu Val Lys Ser Arg 35 40 45 Pro Leu Gly LeuAla Gly Phe Ile Arg Gln Asp Ser Lys Thr Arg Lys 50 55 60 Pro Leu Glu GlnGlu Thr Ile Met Ser Ala Ala Asp Thr Ala Leu Trp 65 70 75 80 Pro Tyr GlyHis Gly Asn Arg Glu His Gln Glu Asn Glu Leu Gln Lys 85 90 95 Tyr Leu GlnTyr Lys Asp Met His Leu Leu Asp Ser Gly Gln Ser Leu 100 105 110 Gly HisThr His Thr Leu Gln Gly Ser His Asn Leu Thr Ala Leu Asn 115 120 125 Ile171 372 PRT Homo sapiens 171 Met Ala Tyr His Ser Phe Leu Val Glu Pro IleSer Cys His Ala Trp 1 5 10 15 Asn Lys Asp Arg Thr Gln Ile Ala Ile CysPro Asn Asn His Glu Val 20 25 30 His Ile Tyr Glu Lys Ser Gly Ala Lys TrpThr Lys Val His Glu Leu 35 40 45 Lys Glu His Asn Gly Gln Val Thr Gly IleAsp Trp Ala Pro Glu Ser 50 55 60 Asn Arg Ile Val Thr Cys Gly Thr Asp ArgAsn Ala Tyr Val Trp Thr 65 70 75 80 Leu Lys Gly Arg Thr Trp Lys Pro ThrLeu Val Ile Leu Arg Ile Asn 85 90 95 Arg Ala Ala Arg Cys Val Arg Trp AlaPro Asn Glu Asn Lys Phe Ala 100 105 110 Val Gly Ser Gly Ser Arg Val IleSer Ile Cys Tyr Phe Glu Gln Glu 115 120 125 Asn Asp Trp Trp Val Cys LysHis Ile Lys Lys Pro Ile Arg Ser Thr 130 135 140 Val Leu Ser Leu Asp TrpHis Pro Asn Asn Val Leu Leu Ala Ala Gly 145 150 155 160 Ser Cys Asp PheLys Cys Arg Ile Phe Ser Ala Tyr Ile Lys Glu Val 165 170 175 Glu Glu ArgPro Ala Pro Thr Pro Trp Gly Ser Lys Met Pro Phe Gly 180 185 190 Glu LeuMet Phe Glu Ser Ser Ser Ser Cys Gly Trp Val His Gly Val 195 200 205 CysPhe Ser Ala Ser Gly Ser Arg Val Ala Trp Val Ser His Asp Ser 210 215 220Thr Val Cys Leu Ala Asp Ala Asp Lys Lys Met Ala Val Ala Thr Leu 225 230235 240 Ala Ser Glu Thr Leu Pro Leu Leu Ala Leu Thr Phe Ile Thr Asp Asn245 250 255 Ser Leu Val Ala Ala Gly His Asp Cys Phe Pro Val Leu Phe ThrTyr 260 265 270 Asp Ala Ala Ala Gly Met Leu Ser Phe Gly Gly Arg Leu AspVal Pro 275 280 285 Lys Gln Ser Ser Gln Arg Gly Leu Thr Ala Arg Glu ArgPhe Gln Asn 290 295 300 Leu Asp Lys Lys Ala Ser Ser Glu Gly Gly Thr AlaAla Gly Ala Gly 305 310 315 320 Leu Asp Ser Leu His Lys Asn Ser Val SerGln Ile Ser Val Leu Ser 325 330 335 Gly Gly Lys Ala Lys Cys Ser Gln PheCys Thr Thr Gly Met Asp Gly 340 345 350 Gly Met Ser Ile Trp Asp Val LysSer Leu Glu Ser Ala Leu Lys Asp 355 360 365 Leu Lys Ile Lys 370 172 216PRT Homo sapiens 172 Met Trp Ser Ile Gly Ala Gly Ala Leu Gly Ala Ala AlaLeu Ala Leu 1 5 10 15 Leu Leu Ala Asn Thr Asp Val Phe Leu Ser Lys ProGln Lys Ala Ala 20 25 30 Leu Glu Tyr Leu Glu Asp Ile Asp Leu Lys Thr LeuGlu Lys Glu Pro 35 40 45 Arg Thr Phe Lys Ala Lys Glu Leu Trp Glu Lys AsnGly Ala Val Ile 50 55 60 Met Ala Val Arg Arg Pro Gly Cys Phe Leu Cys ArgGlu Glu Ala Ala 65 70 75 80 Asp Leu Ser Ser Leu Lys Ser Met Leu Asp GlnLeu Gly Val Pro Leu 85 90 95 Tyr Ala Val Val Lys Glu His Ile Arg Thr GluVal Lys Asp Phe Gln 100 105 110 Pro Tyr Phe Lys Gly Glu Ile Phe Leu AspGlu Lys Lys Lys Phe Tyr 115 120 125 Gly Pro Gln Arg Arg Lys Met Met PheMet Gly Phe Ile Arg Leu Gly 130 135 140 Val Trp Tyr Asn Phe Phe Arg AlaTrp Asn Gly Gly Phe Ser Gly Asn 145 150 155 160 Leu Glu Gly Glu Gly PheIle Leu Gly Gly Val Phe Val Val Gly Ser 165 170 175 Gly Lys Gln Gly IleLeu Leu Glu His Arg Glu Lys Glu Phe Gly Asp 180 185 190 Lys Val Asn LeuLeu Ser Val Leu Glu Ala Ala Lys Met Ile Lys Pro 195 200 205 Gln Thr LeuAla Ser Glu Lys Lys 210 215 173 55 PRT Homo sapiens 173 Met Lys Pro ValSer Arg Arg Thr Leu Asp Trp Ile Tyr Ser Val Leu 1 5 10 15 Leu Leu AlaIle Val Leu Ile Ser Trp Gly Cys Ile Ile Tyr Ala Ser 20 25 30 Met Val SerAla Arg Arg Gln Leu Arg Lys Lys Tyr Pro Asp Lys Ile 35 40 45 Phe Gly ThrAsn Glu Asn Leu 50 55 174 23 PRT Homo sapiens MISC_FEATURE (19) Xaaequals any of the L-amino acids commonly found in naturally occurringproteins 174 Met Ala Ala Asn Thr Phe Val Leu Ile Met Gly Ile Pro Thr SerAla 1 5 10 15 Asn Ala Xaa Arg Asp Leu Phe 20 175 103 PRT Homo sapiens175 Met Ser Ile Cys His Arg Gly Thr Gly Ile Ala Leu Ser Ala Gly Val 1 510 15 Ser Leu Phe Gly Met Ser Ala Leu Leu Leu Pro Gly Asn Phe Glu Ser 2025 30 Tyr Leu Glu Leu Val Lys Ser Leu Cys Leu Gly Pro Ala Leu Ile His 3540 45 Thr Ala Lys Phe Ala Leu Val Phe Pro Leu Met Tyr His Thr Trp Asn 5055 60 Gly Ile Arg His Leu Met Trp Asp Leu Gly Lys Gly Leu Lys Ile Pro 6570 75 80 Gln Leu Tyr Gln Ser Gly Val Val Val Leu Val Leu Thr Val Leu Ser85 90 95 Ser Met Gly Leu Ala Ala Met 100 176 48 PRT Homo sapiens 176 MetThr Lys Ala Ser Ser Leu Trp Pro Leu Lys Thr Thr Cys Gln Ile 1 5 10 15Ser Gly Thr Val Phe Phe Phe Leu Phe Leu Phe Ser Cys Phe Leu Met 20 25 30Gln Ala Gln Cys Asp Lys Phe Val Gly Trp Asp Phe Phe Phe Phe Leu 35 40 45177 96 PRT Homo sapiens MISC_FEATURE (18) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 177 Met Arg Arg AlaLeu Ile Pro Pro Cys Arg Gly Gly Pro Ser Ala Ser 1 5 10 15 Asp Xaa CysCys Ser Cys Ser Pro Ser Gly Phe Ser Ala Gly Arg Gly 20 25 30 Arg Cys ProVal Gln Gly Cys Leu Arg Pro His Arg Val Gln Leu Leu 35 40 45 Arg Arg TrpGly Pro Gly Ser Pro Ala Gly Gln Arg Leu Ser Lys Gly 50 55 60 Phe Gln LeuLeu Arg Trp Trp Gly Pro Gly Ser Pro Ala Pro Glu Pro 65 70 75 80 Arg LysGly Pro Phe Pro Pro Pro Asp Pro Pro Trp Pro Val Thr Leu 85 90 95 178 95PRT Homo sapiens MISC_FEATURE (70) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 178 Met Leu Glu Thr ThrLys His Val Gln Ile Ala Cys Met Leu Leu Leu 1 5 10 15 Thr Cys Gln IlePhe Leu Pro Ser Ser Leu Ser Pro Ser Phe Ile His 20 25 30 Ser Leu Thr AspSer Phe Ile Pro Leu Lys Lys Leu Tyr Val Cys Phe 35 40 45 Val Gln Ser ThrLeu Leu Lys Ala Ala Gly Tyr Lys Ser Ile Ser Glu 50 55 60 Ala Leu Gly PheAsp Xaa Leu Leu Cys Ser Ser Ala Arg Phe Val Trp 65 70 75 80 Ile Cys HisThr Tyr Ser Arg Pro Leu Val Thr Cys Ala Leu His 85 90 95 179 27 PRT Homosapiens 179 Met Ser Val Ile Gly Gly Leu Leu Leu Val Val Ala Leu Gly ProGly 1 5 10 15 Gly Val Ser Met Asp Glu Lys Lys Lys Glu Trp 20 25 180 89PRT Homo sapiens MISC_FEATURE (12) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 180 Met Ser Gly Gly LeuSer Phe Leu Leu Leu Val Xaa Xaa Gly Thr Gln 1 5 10 15 Ser Pro Leu HisLeu Ala Gly Ser Cys Pro Gly Gln Thr His Leu Ser 20 25 30 Phe Pro Leu GlyGln Asp Arg Gly Gln Gln Leu Gln Gln Lys Gln Gln 35 40 45 Asp Leu Glu GlnGlu Gly Leu Glu Ala Thr Gln Gly Leu Leu Ala Gly 50 55 60 Glu Trp Ala ProPro Leu Trp Xaa Leu Gly Ser Leu Phe Gln Ala Phe 65 70 75 80 Val Lys ArgGlu Ser Gln Ala Tyr Ala 85 181 65 PRT Homo sapiens 181 Met Phe Ala AspPhe Ile Val Val Thr Ala Thr Val Gln Arg Cys Pro 1 5 10 15 Gly Ser ProPro Leu Ser Glu Ile Leu Trp Lys Asp Glu Pro Phe Ala 20 25 30 Ile Ser SerHis Ala Gly Leu Pro Trp Leu Ser Ser Trp Pro Ala Pro 35 40 45 Pro Trp ThrTrp Ser Trp Ile Ser Arg Arg Arg Glu His Gly Arg Gly 50 55 60 Ser 65 182105 PRT Homo sapiens 182 Met Ser Ala Leu Thr Arg Leu Ala Ser Phe Ala ArgVal Gly Gly Arg 1 5 10 15 Leu Phe Arg Ser Gly Cys Ala Arg Thr Ala GlyAsp Gly Gly Val Arg 20 25 30 His Ala Gly Gly Gly Val His Ile Glu Pro ArgTyr Arg Gln Phe Pro 35 40 45 Gln Leu Thr Arg Ser Gln Val Phe Gln Ser GluPhe Phe Ser Gly Leu 50 55 60 Met Trp Phe Trp Ile Leu Trp Arg Phe Trp HisAsp Ser Glu Glu Val 65 70 75 80 Leu Gly His Phe Pro Tyr Pro Asp Pro SerGln Trp Thr Asp Glu Glu 85 90 95 Leu Gly Ile Pro Pro Asp Asp Glu Asp 100105 183 132 PRT Homo sapiens 183 Met Asp Val Leu Phe Val Ala Ile Phe AlaVal Pro Leu Ile Leu Gly 1 5 10 15 Gln Glu Tyr Glu Asp Glu Glu Arg LeuGly Glu Asp Glu Tyr Tyr Gln 20 25 30 Val Val Tyr Tyr Tyr Thr Val Thr ProSer Tyr Asp Asp Phe Ser Ala 35 40 45 Asp Phe Thr Ile Asp Tyr Ser Ile PheGlu Ser Glu Asp Arg Leu Asn 50 55 60 Arg Leu Asp Lys Asp Ile Thr Glu AlaIle Glu Thr Thr Ile Ser Leu 65 70 75 80 Glu Thr Ala Arg Ala Asp His ProLys Pro Val Thr Val Lys Pro Val 85 90 95 Thr Thr Glu Pro Gln Ser Pro AspLeu Asn Asp Ala Val Ser Ser Leu 100 105 110 Arg Ser Pro Ile Pro Leu LeuLeu Ser Cys Ala Phe Val Gln Val Gly 115 120 125 Met Tyr Phe Met 130 18469 PRT Homo sapiens 184 Met Pro Cys Gln Pro Gly Gln Val Pro Ser Cys GlnCys Thr Phe Gly 1 5 10 15 Leu Leu Leu Met Leu Pro Ser Leu Pro Ser ProAla Ser Gln Pro Arg 20 25 30 Pro Phe Cys Ser Ser Met Glu Tyr Phe His GlyCys Ala Ser Pro Ser 35 40 45 Gln Ala Ile Ile Gly Gly Phe Pro Phe Ala SerVal Ala Leu Ala Asp 50 55 60 Ile Leu Cys Leu Gln 65 185 45 PRT Homosapiens 185 Met Ser Leu Leu Ser Pro Ala Ile Pro Ala Leu Thr Leu Ile PheIle 1 5 10 15 Leu Met Phe Phe Ser Phe Pro Phe Arg Ala His Thr Val ValThr Ile 20 25 30 Val Ala Ser Gly Phe Leu Gly Leu Ser Pro Leu Cys Gly 3540 45 186 65 PRT Homo sapiens 186 Met Ala Phe Gly Leu Gln Met Phe IleGln Arg Lys Phe Pro Tyr Pro 1 5 10 15 Leu Gln Trp Ser Leu Leu Val AlaVal Val Ala Gly Ser Val Val Ser 20 25 30 Tyr Gly Val Thr Arg Val Glu SerGlu Lys Cys Asn Asn Leu Trp Leu 35 40 45 Phe Leu Glu Thr Gly Gln Leu ProLys Asp Arg Ser Thr Asp Gln Arg 50 55 60 Ser 65 187 49 PRT Homo sapiens187 Met Asn Leu Leu Gly Met Ile Phe Ser Met Cys Gly Leu Met Leu Lys 1 510 15 Leu Lys Trp Cys Ala Trp Val Ala Val Tyr Cys Ser Phe Ile Ser Phe 2025 30 Ala Asn Ser Arg Ser Ser Glu Asp Thr Lys Gln Met Met Ser Ser Phe 3540 45 Met 188 170 PRT Homo sapiens 188 Met Leu Leu Asn Val Ala Leu ValAla Leu Val Leu Leu Gly Ala Tyr 1 5 10 15 Arg Leu Trp Val Arg Trp GlyArg Arg Gly Leu Gly Ala Gly Ala Gly 20 25 30 Ala Gly Glu Glu Ser Pro AlaThr Ser Leu Pro Arg Met Lys Lys Arg 35 40 45 Asp Phe Ser Leu Glu Gln LeuArg Gln Tyr Asp Gly Ser Arg Asn Pro 50 55 60 Arg Ile Leu Leu Ala Val AsnGly Lys Val Phe Asp Val Thr Lys Gly 65 70 75 80 Ser Lys Phe Tyr Gly ProAla Gly Pro Tyr Gly Ile Phe Ala Gly Arg 85 90 95 Asp Ala Ser Arg Gly LeuAla Thr Phe Cys Leu Asp Lys Asp Ala Leu 100 105 110 Arg Asp Glu Tyr AspAsp Leu Ser Asp Leu Asn Ala Val Gln Met Glu 115 120 125 Ser Val Arg GluTrp Glu Met Gln Phe Lys Glu Lys Tyr Asp Tyr Val 130 135 140 Gly Arg LeuLeu Lys Pro Gly Glu Glu Pro Ser Glu Tyr Thr Asp Glu 145 150 155 160 GluAsp Thr Lys Asp His Asn Lys Gln Asp 165 170 189 132 PRT Homo sapiens 189Met Thr Tyr Phe Ser Gly Leu Leu Val Ile Leu Ala Phe Ala Ala Trp 1 5 1015 Val Ala Leu Ala Glu Gly Leu Gly Val Ala Val Tyr Ala Ala Ala Val 20 2530 Leu Leu Gly Ala Gly Cys Ala Thr Ile Leu Val Thr Ser Leu Ala Met 35 4045 Thr Ala Asp Leu Ile Gly Pro His Thr Asn Ser Gly Ala Phe Val Tyr 50 5560 Gly Ser Met Ser Phe Leu Asp Lys Val Ala Asn Gly Leu Ala Val Met 65 7075 80 Ala Ile Gln Ser Leu His Pro Cys Pro Ser Glu Leu Cys Cys Arg Ala 8590 95 Cys Val Ser Phe Tyr His Trp Ala Met Val Ala Val Thr Gly Gly Val100 105 110 Gly Val Ala Ala Ala Leu Cys Leu Cys Ser Leu Leu Leu Trp ProThr 115 120 125 Arg Leu Arg Arg 130 190 92 PRT Homo sapiens 190 Met AlaAla Gly Pro Ser Gly Cys Leu Val Pro Ala Phe Gly Leu Arg 1 5 10 15 LeuLeu Leu Ala Thr Val Leu Gln Ala Val Ser Ala Phe Gly Ala Glu 20 25 30 PheSer Ser Glu Ala Cys Arg Glu Leu Gly Phe Ser Ser Asn Leu Leu 35 40 45 CysSer Ser Cys Asp Leu Leu Gly Gln Phe Asn Leu Leu Gln Leu Asp 50 55 60 ProAsp Cys Arg Gly Cys Cys Gln Glu Glu Ala Gln Phe Glu Thr Lys 65 70 75 80Lys Leu Tyr Ala Gly Ala Ile Leu Glu Val Cys Gly 85 90 191 176 PRT Homosapiens MISC_FEATURE (137) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 191 Met Arg Gly Ser His Leu ArgLeu Leu Pro Tyr Leu Val Ala Ala Asn 1 5 10 15 Pro Val Asn Tyr Gly ArgPro Tyr Arg Leu Ser Cys Val Glu Ala Phe 20 25 30 Ala Ala Thr Phe Cys IleVal Gly Phe Pro Asp Leu Ala Val Ile Leu 35 40 45 Leu Arg Lys Phe Lys TrpGly Lys Gly Phe Leu Asp Leu Asn Arg Gln 50 55 60 Leu Leu Asp Lys Tyr AlaAla Cys Gly Ser Pro Glu Glu Val Leu Gln 65 70 75 80 Ala Glu Gln Glu PheLeu Ala Asn Ala Lys Glu Ser Pro Gln Glu Glu 85 90 95 Glu Ile Asp Pro PheAsp Val Asp Ser Gly Arg Glu Phe Gly Asn Pro 100 105 110 Asn Arg Pro ValAla Ser Thr Arg Leu Pro Ser Asp Thr Asp Asp Ser 115 120 125 Asp Ala SerGlu Asp Pro Gly Pro Xaa Ala Glu Arg Gly Gly Ala Ser 130 135 140 Ser SerCys Cys Glu Glu Glu Gln Thr Gln Gly Arg Gly Ala Glu Ala 145 150 155 160Arg Ala Pro Ala Glu Val Trp Lys Gly Ile Lys Lys Arg Gln Arg Asp 165 170175 192 70 PRT Homo sapiens 192 Met Ser Asn Ala Cys Lys Glu Leu Ala IlePhe Leu Thr Thr Gly Ile 1 5 10 15 Val Val Ser Ala Phe Gly Leu Pro IleVal Phe Ala Arg Ala His Leu 20 25 30 Ile Glu Trp Gly Ala Cys Ala Leu ValLeu Thr Gly Asn Thr Val Ile 35 40 45 Phe Ala Thr Ile Leu Gly Phe Phe LeuVal Phe Gly Ser Asn Asp Asp 50 55 60 Phe Ser Trp Gln Gln Trp 65 70 19325 PRT Homo sapiens MISC_FEATURE (11) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 193 Met Thr Leu LeuIle Ile Phe Leu Pro Phe Xaa Phe Thr Thr Xaa Thr 1 5 10 15 Asn Ser GlyGly Ser Phe Pro Val Arg 20 25 194 73 PRT Homo sapiens MISC_FEATURE (21)Xaa equals any of the L-amino acids commonly found in naturallyoccurring proteins 194 Met Lys Gly Glu Leu Leu Pro Phe Leu Phe Leu ThrVal Trp Leu Trp 1 5 10 15 Leu Tyr Lys Leu Xaa Phe Gly Glu Ser Pro ArgTyr Pro Asn Val Ile 20 25 30 Gly Lys Thr Tyr Phe Phe Phe Trp Thr Asp GlnIle Ser Arg Glu Ser 35 40 45 Arg Phe Leu Glu Arg Leu Ala Phe Ile Val SerGlu Asn Cys Leu Ile 50 55 60 Phe Leu Ile His Ala Ile Thr Gly Gln 65 70195 289 PRT Homo sapiens 195 Met Ser Gly Phe Ser Thr Glu Glu Arg Ala AlaPro Phe Ser Leu Glu 1 5 10 15 Tyr Arg Val Phe Leu Lys Asn Glu Lys GlyGln Tyr Ile Ser Pro Phe 20 25 30 His Asp Ile Pro Ile Tyr Ala Asp Lys AspVal Phe His Met Val Val 35 40 45 Glu Val Pro Arg Trp Ser Asn Ala Lys MetGlu Ile Ala Thr Lys Asp 50 55 60 Pro Leu Asn Pro Ile Lys Gln Asp Val LysLys Gly Lys Leu Arg Tyr 65 70 75 80 Val Ala Asn Leu Phe Pro Tyr Lys GlyTyr Ile Trp Asn Tyr Gly Ala 85 90 95 Ile Pro Gln Thr Trp Glu Asp Pro GlyHis Asn Asp Lys His Thr Gly 100 105 110 Cys Cys Gly Asp Asn Asp Pro IleAsp Val Cys Glu Ile Gly Ser Lys 115 120 125 Val Cys Ala Arg Gly Glu IleIle Gly Val Lys Val Leu Gly Ile Leu 130 135 140 Ala Met Ile Asp Glu GlyGlu Thr Asp Trp Lys Val Ile Ala Ile Asn 145 150 155 160 Val Asp Asp ProAsp Ala Ala Asn Tyr Asn Asp Ile Asn Asp Val Lys 165 170 175 Arg Leu LysPro Gly Tyr Leu Glu Ala Thr Val Asp Trp Phe Arg Arg 180 185 190 Tyr LysVal Pro Asp Gly Lys Pro Glu Asn Glu Phe Ala Phe Asn Ala 195 200 205 GluPhe Lys Asp Lys Asp Phe Ala Ile Asp Ile Ile Lys Ser Thr His 210 215 220Asp His Trp Lys Ala Leu Val Thr Lys Lys Thr Asn Gly Lys Gly Ile 225 230235 240 Ser Cys Met Asn Thr Thr Leu Ser Glu Ser Pro Phe Lys Cys Asp Pro245 250 255 Asp Ala Ala Arg Ala Ile Val Asp Ala Leu Pro Pro Pro Cys GluSer 260 265 270 Ala Cys Thr Val Pro Thr Asp Val Asp Lys Trp Phe His HisGln Lys 275 280 285 Asn 196 624 PRT Homo sapiens 196 Met Glu Ile Pro GlySer Leu Cys Lys Lys Val Lys Leu Ser Asn Asn 1 5 10 15 Ala Gln Asn TrpGly Met Gln Arg Ala Thr Asn Val Thr Tyr Gln Ala 20 25 30 His His Val SerArg Asn Lys Arg Gly Gln Val Val Gly Thr Arg Gly 35 40 45 Gly Phe Arg GlyCys Thr Val Trp Leu Thr Gly Leu Ser Gly Ala Gly 50 55 60 Lys Thr Thr ValSer Met Ala Leu Glu Glu Tyr Leu Val Cys His Gly 65 70 75 80 Ile Pro CysTyr Thr Leu Asp Gly Asp Asn Ile Arg Gln Gly Leu Asn 85 90 95 Lys Asn LeuGly Phe Ser Pro Glu Asp Arg Glu Glu Asn Val Arg Arg 100 105 110 Ile AlaGlu Val Ala Lys Leu Phe Ala Asp Ala Gly Leu Val Cys Ile 115 120 125 ThrSer Phe Ile Ser Pro Tyr Thr Gln Asp Arg Asn Asn Ala Arg Gln 130 135 140Ile His Glu Gly Ala Ser Leu Pro Phe Phe Glu Val Phe Val Asp Ala 145 150155 160 Pro Leu His Val Cys Glu Gln Arg Asp Val Lys Gly Leu Tyr Lys Lys165 170 175 Ala Arg Ala Gly Glu Ile Lys Gly Phe Thr Gly Ile Asp Ser GluTyr 180 185 190 Glu Lys Pro Glu Ala Pro Glu Leu Val Leu Lys Thr Asp SerCys Asp 195 200 205 Val Asn Asp Cys Val Gln Gln Val Val Glu Leu Leu GlnGlu Arg Asp 210 215 220 Ile Val Pro Val Asp Ala Ser Tyr Glu Val Lys GluLeu Tyr Val Pro 225 230 235 240 Glu Asn Lys Leu His Leu Ala Lys Thr AspAla Glu Thr Leu Pro Ala 245 250 255 Leu Lys Ile Asn Lys Val Asp Met GlnTrp Val Gln Val Leu Ala Glu 260 265 270 Gly Trp Ala Thr Pro Leu Asn GlyPhe Met Arg Glu Arg Glu Tyr Leu 275 280 285 Gln Cys Leu His Phe Asp CysLeu Leu Asp Gly Gly Val Ile Asn Leu 290 295 300 Ser Val Pro Ile Val LeuThr Ala Thr His Glu Asp Lys Glu Arg Leu 305 310 315 320 Asp Gly Cys ThrAla Phe Ala Leu Met Tyr Glu Gly Arg Arg Val Ala 325 330 335 Ile Leu ArgAsn Pro Glu Phe Phe Glu His Arg Lys Glu Glu Arg Cys 340 345 350 Ala ArgGln Trp Gly Thr Thr Cys Lys Asn His Pro Tyr Ile Lys Met 355 360 365 ValMet Glu Gln Gly Asp Trp Leu Ile Gly Gly Asp Leu Gln Val Leu 370 375 380Asp Arg Val Tyr Trp Asn Asp Gly Leu Asp Gln Tyr Arg Leu Thr Pro 385 390395 400 Thr Glu Leu Lys Gln Lys Phe Lys Asp Met Asn Ala Asp Ala Val Phe405 410 415 Ala Phe Gln Leu Arg Asn Pro Val His Asn Gly His Ala Leu LeuMet 420 425 430 Gln Asp Thr His Lys Gln Leu Leu Glu Arg Gly Tyr Arg ArgPro Val 435 440 445 Leu Leu Leu His Pro Leu Gly Gly Trp Thr Lys Asp AspAsp Val Pro 450 455 460 Leu Met Trp Arg Met Lys Gln His Ala Ala Val LeuGlu Glu Gly Val 465 470 475 480 Leu Asn Pro Glu Thr Thr Val Val Ala IlePhe Pro Ser Pro Met Met 485 490 495 Tyr Ala Gly Pro Thr Glu Val Gln TrpHis Cys Arg Ala Arg Met Val 500 505 510 Ala Gly Ala Asn Phe Tyr Ile ValGly Arg Asp Pro Ala Gly Met Pro 515 520 525 His Pro Glu Thr Gly Lys AspLeu Tyr Glu Pro Ser His Gly Ala Lys 530 535 540 Val Leu Thr Met Ala ProGly Leu Ile Thr Leu Glu Ile Val Pro Phe 545 550 555 560 Arg Val Ala AlaTyr Asn Lys Lys Lys Lys Arg Met Asp Tyr Tyr Asp 565 570 575 Ser Glu HisHis Glu Asp Phe Glu Phe Ile Ser Gly Thr Arg Met Arg 580 585 590 Lys LeuAla Arg Glu Gly Gln Lys Pro Pro Glu Gly Phe Met Ala Pro 595 600 605 LysAla Trp Thr Val Leu Thr Glu Tyr Tyr Lys Ser Leu Glu Lys Ala 610 615 620197 649 PRT Homo sapiens MISC_FEATURE (555) Xaa equals any of theL-amino acids commonly found in naturally occurring proteins 197 Met SerAla Ser Gln Asp Leu Glu Pro Lys Pro Leu Phe Pro Lys Pro 1 5 10 15 AlaPhe Gly Gln Lys Pro Pro Leu Ser Thr Glu Asn Ser His Glu Asp 20 25 30 GluSer Pro Met Lys Asn Val Ser Ser Ser Lys Gly Ser Pro Ala Pro 35 40 45 LeuGly Val Arg Ser Lys Ser Gly Pro Leu Lys Pro Ala Arg Glu Asp 50 55 60 SerGlu Asn Lys Asp His Ala Gly Glu Ile Ser Ser Leu Pro Phe Pro 65 70 75 80Gly Val Val Leu Lys Pro Ala Ala Ser Arg Gly Gly Pro Gly Leu Ser 85 90 95Lys Asn Gly Glu Glu Lys Lys Glu Asp Arg Lys Ile Asp Ala Ala Lys 100 105110 Asn Thr Phe Gln Ser Lys Ile Asn Gln Glu Glu Leu Ala Ser Gly Thr 115120 125 Pro Pro Ala Arg Phe Pro Lys Ala Pro Ser Lys Leu Thr Val Gly Gly130 135 140 Pro Trp Gly Gln Ser Gln Glu Lys Glu Lys Gly Asp Lys Asn SerAla 145 150 155 160 Thr Pro Lys Gln Lys Pro Leu Pro Pro Leu Phe Thr LeuGly Pro Pro 165 170 175 Pro Pro Lys Pro Asn Arg Pro Pro Asn Val Asp LeuThr Lys Phe His 180 185 190 Lys Thr Ser Ser Gly Asn Ser Thr Ser Lys GlyGln Thr Ser Tyr Ser 195 200 205 Thr Thr Ser Leu Pro Pro Pro Pro Pro SerHis Pro Ala Ser Gln Pro 210 215 220 Pro Leu Pro Ala Ser His Pro Ser GlnPro Pro Val Pro Ser Leu Pro 225 230 235 240 Pro Arg Asn Ile Lys Pro ProPhe Asp Leu Lys Ser Pro Val Asn Glu 245 250 255 Asp Asn Gln Asp Gly ValThr His Ser Asp Gly Ala Gly Asn Leu Asp 260 265 270 Glu Glu Gln Asp SerGlu Gly Glu Thr Tyr Glu Asp Ile Glu Ala Ser 275 280 285 Lys Glu Arg GluLys Lys Arg Glu Lys Glu Glu Lys Lys Arg Leu Glu 290 295 300 Leu Glu LysLys Glu Gln Lys Glu Lys Glu Lys Lys Glu Gln Glu Ile 305 310 315 320 LysLys Lys Phe Lys Leu Thr Gly Pro Ile Gln Val Ile His Leu Ala 325 330 335Lys Ala Cys Cys Asp Val Lys Gly Gly Lys Asn Glu Leu Ser Phe Lys 340 345350 Gln Gly Glu Gln Ile Glu Ile Ile Arg Ile Thr Asp Asn Pro Glu Gly 355360 365 Lys Trp Leu Gly Arg Thr Ala Arg Gly Ser Tyr Gly Tyr Ile Lys Thr370 375 380 Thr Ala Val Glu Ile Asp Tyr Asp Ser Leu Lys Leu Lys Lys AspSer 385 390 395 400 Leu Gly Ala Pro Ser Arg Pro Ile Glu Asp Asp Gln GluVal Tyr Asp 405 410 415 Asp Val Ala Glu Gln Asp Asp Ile Ser Ser His SerGln Ser Gly Ser 420 425 430 Gly Gly Ile Phe Pro Pro Pro Pro Asp Asp AspIle Tyr Asp Gly Ile 435 440 445 Glu Glu Glu Asp Ala Asp Asp Gly Ser ThrLeu Gln Val Gln Glu Lys 450 455 460 Ser Asn Thr Trp Ser Trp Gly Ile LeuLys Met Leu Lys Gly Lys Asp 465 470 475 480 Asp Arg Lys Lys Ser Ile ArgGlu Lys Pro Lys Val Ser Asp Ser Asp 485 490 495 Asn Asn Glu Gly Ser SerPhe Pro Ala Pro Pro Lys Gln Leu Asp Met 500 505 510 Gly Asp Glu Val TyrAsp Asp Val Asp Thr Ser Asp Phe Pro Val Ser 515 520 525 Ser Ala Glu MetSer Gln Gly Thr Asn Val Gly Lys Ala Lys Thr Glu 530 535 540 Glu Lys AspLeu Lys Lys Leu Lys Lys Gln Xaa Lys Xaa Xaa Lys Asp 545 550 555 560 PheArg Lys Lys Phe Lys Tyr Asp Gly Glu Ile Arg Val Leu Tyr Ser 565 570 575Thr Lys Val Thr Thr Ser Ile Thr Ser Lys Lys Trp Gly Thr Arg Asp 580 585590 Leu Gln Val Lys Pro Gly Glu Ser Leu Glu Val Ile Gln Thr Thr Asp 595600 605 Asp Thr Lys Val Leu Cys Arg Asn Glu Glu Gly Lys Tyr Gly Tyr Val610 615 620 Leu Arg Ser Tyr Leu Ala Asp Asn Asp Gly Glu Ile Tyr Asp AspIle 625 630 635 640 Ala Asp Gly Cys Ile Tyr Asp Asn Asp 645 198 55 PRTHomo sapiens 198 Met Ala Trp Pro Ser Arg Ser Lys Met Phe Thr Leu Leu ProVal Leu 1 5 10 15 Cys Tyr Leu Trp Ser Leu Trp Leu Pro Gln Phe Ser TrpIle Gln Glu 20 25 30 Leu Lys Ala Val Leu Arg Asp Asp Gly Leu Ile Ser AlaVal Ala Trp 35 40 45 Asn Ala Glu Phe Gln Thr Cys 50 55 199 266 PRT Homosapiens 199 Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu AlaLys 1 5 10 15 Lys Asp Glu Pro Lys Ser Gly Glu Glu Ala Leu Ile Ile ProPro Asp 20 25 30 Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val ProVal Gly 35 40 45 Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu AlaPhe Met 50 55 60 Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys TyrPhe Ala 65 70 75 80 Leu Gln Pro Asp Asp Val Tyr Tyr Cys Gly Ile Lys TyrIle Lys Asp 85 90 95 Asp Val Ile Leu Asn Glu Pro Ser Ala Asp Ala Pro AlaAla Leu Tyr 100 105 110 Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu GluGlu Glu Val Glu 115 120 125 Phe Ile Ser Val Pro Val Pro Glu Phe Ala AspSer Asp Pro Ala Asn 130 135 140 Ile Val His Asp Phe Asn Lys Lys Leu ThrAla Tyr Leu Asp Leu Asn 145 150 155 160 Leu Asp Lys Cys Tyr Val Ile ProLeu Asn Thr Ser Ile Val Met Pro 165 170 175 Pro Arg Asn Leu Leu Glu LeuLeu Ile Asn Ile Lys Ala Gly Thr Tyr 180 185 190 Leu Pro Gln Ser Tyr LeuIle His Glu His Met Val Ile Thr Asp Arg 195 200 205 Ile Glu Asn Ile AspHis Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 210 215 220 Asp Lys Glu ThrTyr Lys Leu Gln Arg Arg Glu Thr Ile Lys Gly Ile 225 230 235 240 Gln LysArg Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn 245 250 255 LysPhe Ala Val Glu Thr Leu Ile Cys Ser 260 265 200 315 PRT Homo sapiens 200Met Asp Leu Arg Gln Phe Leu Met Cys Leu Ser Leu Cys Thr Ala Phe 1 5 1015 Ala Leu Ser Lys Pro Thr Glu Lys Lys Asp Arg Val His His Glu Pro 20 2530 Gln Leu Ser Asp Lys Val His Asn Asp Ala Gln Ser Phe Asp Tyr Asp 35 4045 His Asp Ala Phe Leu Gly Ala Glu Glu Ala Lys Thr Phe Asp Gln Leu 50 5560 Thr Pro Glu Glu Ser Lys Glu Arg Leu Gly Lys Ile Val Ser Lys Ile 65 7075 80 Asp Gly Asp Lys Asp Gly Phe Val Thr Val Asp Glu Leu Lys Asp Trp 8590 95 Ile Lys Phe Ala Gln Lys Arg Trp Ile Tyr Glu Asp Val Glu Arg Gln100 105 110 Trp Lys Gly His Asp Leu Asn Glu Asp Gly Leu Val Ser Trp GluGlu 115 120 125 Tyr Lys Asn Ala Thr Tyr Gly Tyr Val Leu Asp Asp Pro AspPro Asp 130 135 140 Asp Gly Phe Asn Tyr Lys Gln Met Met Val Arg Asp GluArg Arg Phe 145 150 155 160 Lys Met Ala Asp Lys Asp Gly Asp Leu Ile AlaThr Lys Glu Glu Phe 165 170 175 Thr Ala Phe Leu His Pro Glu Glu Tyr AspTyr Met Lys Asp Ile Val 180 185 190 Val Gln Glu Thr Met Glu Asp Ile AspLys Asn Ala Asp Gly Phe Ile 195 200 205 Asp Leu Glu Glu Tyr Ile Gly AspMet Tyr Ser His Asp Gly Asn Thr 210 215 220 Asp Glu Pro Glu Trp Val LysThr Glu Arg Glu Gln Phe Val Glu Phe 225 230 235 240 Arg Asp Lys Asn ArgAsp Gly Lys Met Asp Lys Glu Glu Thr Lys Asp 245 250 255 Trp Ile Leu ProSer Asp Tyr Asp His Ala Glu Ala Glu Ala Arg His 260 265 270 Leu Val TyrGlu Ser Asp Gln Asn Lys Asp Gly Lys Leu Thr Lys Glu 275 280 285 Glu IleVal Asp Lys Tyr Asp Leu Phe Val Gly Ser Gln Ala Thr Asp 290 295 300 PheGly Glu Ala Leu Val Arg His Asp Glu Phe 305 310 315 201 207 PRT Homosapiens 201 Met Phe Asp Ala Val Leu Ile Leu Leu Leu Ile Pro Leu Lys AspLys 1 5 10 15 Leu Val Asp Pro Ile Leu Arg Arg His Gly Leu Leu Pro SerSer Leu 20 25 30 Lys Arg Ile Ala Val Gly Met Phe Phe Val Met Cys Ser AlaPhe Ala 35 40 45 Ala Gly Ile Leu Glu Ser Lys Arg Leu Asn Leu Val Lys GluLys Thr 50 55 60 Ile Asn Gln Thr Ile Gly Asn Val Val Tyr His Ala Ala AspLeu Ser 65 70 75 80 Leu Trp Trp Gln Val Pro Gln Tyr Leu Leu Ile Gly IleSer Glu Ile 85 90 95 Phe Ala Ser Ile Ala Gly Leu Glu Phe Ala Tyr Ser AlaAla Pro Lys 100 105 110 Ser Met Gln Ser Ala Ile Met Gly Leu Phe Phe PhePhe Ser Gly Val 115 120 125 Gly Ser Phe Val Gly Ser Gly Leu Leu Ala LeuVal Ser Ile Lys Ala 130 135 140 Ile Gly Trp Met Ser Ser His Thr Asp PheGly Asn Ile Asn Gly Cys 145 150 155 160 Tyr Leu Asn Tyr Tyr Phe Phe LeuLeu Ala Ala Ile Gln Gly Ala Thr 165 170 175 Leu Leu Leu Phe Leu Ile IleSer Val Lys Tyr Asp His His Arg Asp 180 185 190 His Gln Arg Ser Arg AlaAsn Gly Val Pro Thr Ser Arg Arg Ala 195 200 205 202 195 PRT Homo sapiens202 Met Arg Ser Arg Ile Arg Glu Phe Asp Ser Ser Thr Leu Asn Glu Ser 1 510 15 Val Arg Asn Thr Ile Met Arg Asp Leu Lys Ala Val Gly Lys Lys Phe 2025 30 Met His Val Leu Tyr Pro Arg Lys Ser Asn Thr Leu Leu Arg Asp Trp 3540 45 Asp Leu Trp Gly Pro Leu Ile Leu Cys Val Thr Leu Ala Leu Met Leu 5055 60 Gln Arg Asp Ser Ala Asp Ser Glu Lys Asp Gly Gly Pro Gln Phe Ala 6570 75 80 Glu Val Phe Val Ile Val Trp Phe Gly Ala Val Thr Ile Thr Leu Asn85 90 95 Ser Lys Leu Leu Gly Gly Asn Ile Ser Phe Phe Gln Ser Leu Cys Val100 105 110 Leu Gly Tyr Cys Ile Leu Pro Leu Thr Val Ala Met Leu Ile CysArg 115 120 125 Leu Val Leu Leu Ala Asp Pro Gly Pro Val Asn Phe Met ValArg Leu 130 135 140 Phe Val Val Ile Val Met Phe Ala Trp Ser Ile Val AlaSer Thr Ala 145 150 155 160 Phe Leu Ala Asp Ser Gln Pro Pro Asn Arg ArgAla Leu Ala Val Tyr 165 170 175 Pro Val Phe Leu Phe Tyr Phe Val Ile SerTrp Met Ile Leu Thr Phe 180 185 190 Thr Pro Gln 195 203 330 PRT Homosapiens 203 Met Ala Lys Asp Gln Ala Val Glu Asn Ile Leu Val Ser Pro ValVal 1 5 10 15 Val Ala Ser Ser Leu Gly Leu Val Ser Leu Gly Gly Lys AlaThr Thr 20 25 30 Ala Ser Gln Ala Lys Ala Val Leu Ser Ala Glu Gln Leu ArgAsp Glu 35 40 45 Glu Val His Ala Gly Leu Gly Glu Leu Leu Arg Ser Leu SerAsn Ser 50 55 60 Thr Ala Arg Asn Val Thr Trp Lys Leu Gly Ser Arg Leu TyrGly Pro 65 70 75 80 Ser Ser Val Ser Phe Ala Asp Asp Phe Val Arg Ser SerLys Gln His 85 90 95 Tyr Asn Cys Glu His Ser Lys Ile Asn Phe Arg Asp LysArg Ser Ala 100 105 110 Leu Gln Ser Ile Asn Glu Trp Ala Ala Gln Thr ThrAsp Gly Lys Leu 115 120 125 Pro Glu Val Thr Lys Asp Val Glu Arg Thr AspGly Ala Leu Leu Val 130 135 140 Asn Ala Met Phe Phe Lys Pro His Trp AspGlu Lys Phe His His Lys 145 150 155 160 Met Val Asp Asn Arg Gly Phe MetVal Thr Arg Ser Tyr Thr Val Gly 165 170 175 Val Met Met Met His Arg ThrGly Leu Tyr Asn Tyr Tyr Asp Asp Glu 180 185 190 Lys Glu Lys Leu Gln IleVal Glu Met Pro Leu Ala His Lys Leu Ser 195 200 205 Ser Leu Ile Ile LeuMet Pro His His Val Glu Pro Leu Glu Arg Leu 210 215 220 Glu Lys Leu LeuThr Lys Glu Gln Leu Lys Ile Trp Met Gly Lys Met 225 230 235 240 Gln LysLys Ala Val Ala Ile Ser Leu Pro Lys Gly Val Val Glu Val 245 250 255 ThrHis Asp Leu Gln Lys His Leu Ala Gly Leu Gly Leu Thr Glu Ala 260 265 270Ile Asp Lys Asn Lys Ala Asp Leu Ser Arg Met Ser Gly Lys Lys Asp 275 280285 Leu Tyr Leu Ala Ser Val Phe His Ala Thr Ala Phe Glu Leu Asp Thr 290295 300 Asp Gly Asn Pro Leu Thr Arg Ile Thr Gly Gly Gly Val Arg Thr Gln305 310 315 320 Val Phe Tyr Ala Asp His Pro Phe Ile Ser 325 330 204 58PRT Homo sapiens 204 Met Cys Met Gln Leu Phe Gly Phe Leu Ala Phe Met IlePhe Met Cys 1 5 10 15 Trp Val Gly Asp Val Tyr Pro Val Tyr Gln Pro ValGly Pro Lys Gln 20 25 30 Tyr Pro Tyr Asn Asn Leu Tyr Leu Glu Arg Gly GlyAsp Pro Ser Lys 35 40 45 Glu Pro Glu Arg Val Val His Tyr Glu Ile 50 55205 392 PRT Homo sapiens 205 Met Asp Ala Leu Val Glu Asp Asp Ile Cys IleLeu Asn His Glu Lys 1 5 10 15 Ala His Lys Arg Asp Thr Val Thr Pro ValSer Ile Tyr Ser Gly Asp 20 25 30 Glu Ser Val Ala Ser His Phe Ala Leu ValThr Ala Tyr Glu Asp Ile 35 40 45 Lys Lys Arg Leu Lys Asp Ser Glu Lys GluAsn Ser Leu Leu Lys Lys 50 55 60 Arg Ile Arg Phe Leu Glu Glu Lys Leu IleAla Arg Phe Glu Glu Glu 65 70 75 80 Thr Ser Ser Val Gly Arg Glu Gln ValAsn Lys Ala Tyr His Ala Tyr 85 90 95 Arg Glu Val Cys Ile Asp Arg Asp AsnLeu Lys Ser Lys Leu Asp Lys 100 105 110 Met Asn Lys Asp Asn Ser Glu SerLeu Lys Val Leu Asn Glu Gln Leu 115 120 125 Gln Ser Lys Glu Val Glu LeuLeu Gln Leu Arg Thr Glu Val Glu Thr 130 135 140 Gln Gln Val Met Arg AsnLeu Asn Pro Pro Ser Ser Asn Trp Glu Val 145 150 155 160 Glu Lys Leu SerCys Asp Leu Lys Ile His Gly Leu Glu Gln Glu Leu 165 170 175 Glu Leu MetArg Lys Glu Cys Ser Asp Leu Lys Ile Glu Leu Gln Lys 180 185 190 Ala LysGln Thr Asp Pro Tyr Gln Glu Asp Asn Leu Lys Ser Arg Asp 195 200 205 LeuGln Lys Leu Ser Ile Ser Ser Asp Asn Met Gln His Ala Tyr Trp 210 215 220Glu Leu Lys Arg Glu Met Ser Asn Leu His Leu Val Thr Gln Val Gln 225 230235 240 Ala Glu Leu Leu Arg Lys Leu Lys Thr Ser Thr Ala Ile Lys Lys Ala245 250 255 Cys Ala Pro Val Gly Cys Ser Glu Asp Leu Gly Arg Asp Ser ThrLys 260 265 270 Leu His Leu Met Asn Phe Thr Ala Thr Tyr Thr Arg His ProPro Leu 275 280 285 Leu Pro Asn Gly Lys Ala Leu Cys His Thr Thr Ser SerPro Leu Pro 290 295 300 Gly Asp Val Lys Val Leu Ser Glu Lys Ala Ile LeuGln Ser Trp Thr 305 310 315 320 Asp Asn Glu Arg Ser Ile Pro Asn Asp GlyThr Cys Phe Gln Glu His 325 330 335 Ser Ser Tyr Gly Arg Asn Ser Leu GluAsp Asn Ser Trp Val Phe Pro 340 345 350 Ser Pro Pro Lys Ser Ser Glu ThrAla Phe Gly Glu Thr Lys Thr Lys 355 360 365 Thr Leu Pro Leu Pro Asn LeuPro Pro Leu His Tyr Leu Asp Gln His 370 375 380 Asn Gln Asn Cys Leu TyrLys Asn 385 390 206 26 PRT Homo sapiens 206 Met His His His Thr Gln LeuMet Phe Ile Tyr Leu Phe Ile Tyr Leu 1 5 10 15 Phe Ile Leu Gly Val PhePhe Phe Phe Phe 20 25 207 38 PRT Homo sapiens 207 Met Asn Cys Ile LeuLeu Leu Tyr Leu Leu Ile Pro Thr Ile Ser Ile 1 5 10 15 Ser Val Val ProTyr Val Ala Leu Asn Ile Lys Tyr Ile Lys Glu Cys 20 25 30 Thr Glu Asn SerPhe Tyr 35 208 45 PRT Homo sapiens MISC_FEATURE (28) Xaa equals any ofthe L-amino acids commonly found in naturally occurring proteins 208 MetLys Lys Ser Leu Glu Asn Leu Asn Arg Leu Gln Val Met Leu Leu 1 5 10 15His Leu Thr Ala Ala Phe Leu Gln Arg Ala His Xaa Ile Leu Thr Thr 20 25 30Arg Met Ser Leu Gly Phe Gln Ser Pro His Leu Thr Met 35 40 45 209 81 PRTHomo sapiens 209 Met Ser Lys Arg Ser Ala Ser Phe Ile Leu Leu Pro Leu LeuPhe Leu 1 5 10 15 Lys Gly Ser Phe Ala Lys Leu Asn Ala Arg Ile Ser AspCys Leu Glu 20 25 30 Glu Arg Tyr Cys His Asn Leu Trp Met Val Phe Gln GlyCys Val Ile 35 40 45 Thr Glu Leu His Leu Ser Arg Met Ser Lys Thr Leu SerSer Leu Cys 50 55 60 Tyr Asp Phe Val Ile Asn Val Tyr Ile Phe Phe Lys PheLeu Asp Ile 65 70 75 80 Thr 210 49 PRT Homo sapiens 210 Met Cys Ser LeuPhe Glu Ser Arg Phe Phe Cys Phe Val Leu Phe Ser 1 5 10 15 Glu Lys IleIle Gln Leu Cys Ala Ser Ile Ala Phe Leu Cys Phe Val 20 25 30 Lys His ValPro Trp Pro Lys Trp Lys Arg Lys Cys Leu Ile Asn Ala 35 40 45 Phe 211 203PRT Homo sapiens 211 Met Thr Leu Arg Pro Ser Leu Leu Pro Leu His Leu LeuLeu Leu Leu 1 5 10 15 Leu Leu Ser Ala Ala Val Cys Arg Ala Glu Ala GlyLeu Glu Thr Glu 20 25 30 Ser Pro Val Arg Thr Leu Gln Val Glu Thr Leu ValGlu Pro Pro Glu 35 40 45 Pro Cys Ala Glu Pro Ala Ala Phe Gly Asp Thr LeuHis Ile His Tyr 50 55 60 Thr Gly Ser Leu Val Asp Gly Arg Ile Ile Asp ThrSer Leu Thr Arg 65 70 75 80 Asp Pro Leu Val Ile Glu Leu Gly Gln Lys GlnVal Ile Pro Gly Leu 85 90 95 Glu Gln Ser Leu Leu Asp Met Cys Val Gly GluLys Arg Arg Ala Ile 100 105 110 Ile Pro Ser His Leu Ala Tyr Gly Lys ArgGly Phe Pro Pro Ser Val 115 120 125 Pro Ala Asp Ala Val Val Gln Tyr AspVal Glu Leu Ile Ala Leu Ile 130 135 140 Arg Ala Asn Tyr Trp Leu Lys LeuVal Lys Gly Ile Leu Pro Leu Val 145 150 155 160 Gly Met Ala Met Val ProPro Ser Trp Ala Ser Leu Gly Ile Thr Tyr 165 170 175 Thr Glu Arg Pro IleAsp Pro Lys Ser Pro Lys Arg Ser Ser Arg Lys 180 185 190 Arg Asn Glu ThrArg Ala Lys Arg Asn Asn Lys 195 200 212 186 PRT Homo sapiensMISC_FEATURE (122) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 212 Met Lys Thr Leu Met Thr Ile Cys Pro GlyThr Val Leu Leu Val Phe 1 5 10 15 Ser Ile Ser Leu Trp Ile Ile Ala AlaTrp Thr Val Arg Val Cys Glu 20 25 30 Ser Pro Glu Ser Pro Ala Gln Pro SerGly Ser Ser Leu Pro Ala Trp 35 40 45 Tyr His Asp Gln Gln Asp Val Thr SerAsn Phe Leu Gly Ala Met Trp 50 55 60 Leu Ile Ser Ile Thr Phe Leu Ser IleGly Tyr Gly Asp Met Val Pro 65 70 75 80 His Thr Tyr Cys Gly Lys Gly ValCys Leu Leu Thr Gly Ile Met Gly 85 90 95 Ala Gly Cys Thr Ala Leu Val ValAla Val Val Ala Arg Lys Leu Glu 100 105 110 Leu Thr Lys Ala Glu Lys HisVal His Xaa Phe Met Met Asp Thr Gln 115 120 125 Leu Thr Lys Arg Ile LysAsn Xaa Ala Ala Asn Val Leu Xaa Glu Thr 130 135 140 Trp Leu Ile Tyr LysHis Thr Lys Leu Leu Lys Lys Ile Asp His Ala 145 150 155 160 Lys Val ArgAsn Thr Arg Gly Ser Ser Ser Lys Tyr Pro Pro Val Glu 165 170 175 Glu ArgGln Asp Gly Thr Glu Glu Ala Glu 180 185 213 90 PRT Homo sapiens 213 MetLys Phe Leu Ala Val Leu Val Leu Leu Gly Val Ser Ile Phe Leu 1 5 10 15Val Ser Ala Gln Asn Pro Thr Thr Ala Ala Pro Ala Asp Thr Tyr Pro 20 25 30Ala Thr Gly Pro Ala Asp Asp Glu Ala Pro Asp Ala Glu Thr Thr Ala 35 40 45Ala Ala Thr Thr Ala Thr Thr Ala Ala Pro Thr Thr Ala Thr Thr Ala 50 55 60Ala Ser Thr Thr Ala Arg Lys Asp Ile Pro Val Leu Pro Lys Trp Val 65 70 7580 Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 85 90 214 48 PRT Homo sapiens214 Met Ser Ser Ala Ala Ala Asp His Trp Ala Trp Leu Leu Val Leu Ser 1 510 15 Phe Val Phe Gly Cys Asn Val Leu Arg Ile Leu Leu Pro Ser Phe Ser 2025 30 Ser Phe Met Ser Arg Val Leu Gln Lys Asp Ala Asp Arg Ser His Arg 3540 45 215 70 PRT Homo sapiens 215 Met Thr Ala Pro Leu Pro Pro Leu SerGly Leu Ala Leu Phe Leu Ile 1 5 10 15 Val Phe Phe Ser Leu Gly Val PheCys Ile Cys His Ser His Trp Tyr 20 25 30 His Thr Leu Gln Gln Met Ala GlyThr Glu Pro Lys Ala Leu Leu Leu 35 40 45 Ser Pro Pro Ala Ala Thr Thr PheVal Thr Val Thr His Glu Val Trp 50 55 60 Lys Glu Gln Ala Leu Ala 65 70216 83 PRT Homo sapiens 216 Met Thr Cys Ser Val Ala Leu Leu Leu Ile LeuGly Leu Arg Cys Ser 1 5 10 15 Gly Val Arg Pro Gly Leu Val Gly Glu GlyHis Asn Pro Ser Leu Leu 20 25 30 Val Cys Leu Leu Leu Lys Asp Ser Arg ThrAsn Gln Gly Ser Cys Pro 35 40 45 Gly Gly Pro Trp Ser Glu Arg Asp Ile GluSer Val Thr Ser Asp Asn 50 55 60 Cys Glu Ala Thr Leu Gly Tyr Arg Asn HisSer Leu Pro Ser Asn Tyr 65 70 75 80 Tyr Asn Ser 217 43 PRT Homo sapiens217 Met Leu Thr Arg Ser Leu Lys Thr Leu Pro Ser Ala Cys Thr Ala Phe 1 510 15 Leu Leu Leu Phe Phe Leu Phe Ser Ser Gly Asp Pro Glu Leu Ser Cys 2025 30 Ser Cys Thr Leu Arg Thr Gln Ser Ser Trp Ser 35 40 218 184 PRT Homosapiens MISC_FEATURE (140) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 218 Met Trp Arg Pro Ser Val LeuLeu Leu Leu Leu Leu Leu Arg His Gly 1 5 10 15 Ala Gln Gly Lys Pro SerPro Asp Ala Gly Pro His Gly Gln Gly Arg 20 25 30 Val His Gln Ala Ala ProLeu Ser Asp Ala Pro His Asp Asp Ala His 35 40 45 Gly Asn Phe Gln Tyr AspHis Glu Ala Phe Leu Gly Arg Glu Val Ala 50 55 60 Lys Glu Phe Asp Gln LeuThr Pro Glu Glu Ser Gln Ala Arg Leu Gly 65 70 75 80 Arg Ile Val Asp ArgMet Asp Arg Ala Gly Asp Gly Asp Gly Trp Val 85 90 95 Ser Leu Ala Glu LeuArg Ala Trp Ile Ala His Thr Gln Gln Arg His 100 105 110 Ile Arg Asp SerVal Ser Ala Ala Trp Asp Thr Tyr Asp Thr Asp Arg 115 120 125 Asp Gly ArgVal Gly Trp Glu Glu Leu Arg Asn Xaa Thr Tyr Gly His 130 135 140 Xaa XaaPro Xaa Glu Glu Phe His Asp Val Glu Asp Ala Glu Thr Tyr 145 150 155 160Lys Lys Met Leu Xaa Arg Asp Glu Arg Arg Phe Arg Val Ala Asp Gln 165 170175 Asp Gly Asp Ser Met Ala Thr Arg 180 219 71 PRT Homo sapiensMISC_FEATURE (40) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 219 Met Trp Leu Phe Ile Leu Leu Ser Leu AlaLeu Ile Ser Asp Ala Met 1 5 10 15 Val Met Asp Glu Lys Val Lys Arg SerLeu Cys Trp Thr Arg Leu Leu 20 25 30 Pro Ser Ala Thr Thr Met Pro Xaa ThrArg Ile Thr Pro Asn Thr Gly 35 40 45 Ala Glu Xaa Ile Ser Val Xaa Thr AlaThr Ser Ser Pro Ser Pro Leu 50 55 60 Thr Ala Pro Ile Met Trp Pro 65 70220 10 PRT Homo sapiens 220 Met His Val Phe Val Leu Glu Ile Phe Leu 1 510 221 138 PRT Homo sapiens 221 Met Ala Val Ala Thr Leu Ala Ser Glu ThrLeu Pro Leu Leu Ala Leu 1 5 10 15 Thr Phe Ile Thr Asp Asn Ser Leu ValAla Ala Gly His Asp Cys Phe 20 25 30 Pro Val Leu Phe Thr Tyr Asp Ala AlaAla Gly Met Leu Ser Phe Gly 35 40 45 Gly Arg Leu Asp Val Pro Lys Gln SerSer Gln Arg Gly Leu Thr Ala 50 55 60 Arg Glu Arg Phe Gln Asn Leu Asp LysLys Ala Ser Ser Glu Gly Gly 65 70 75 80 Thr Ala Ala Gly Ala Gly Leu AspSer Leu His Lys Asn Ser Val Ser 85 90 95 Gln Ile Ser Val Leu Ser Gly GlyLys Ala Lys Cys Ser Gln Phe Cys 100 105 110 Thr Thr Gly Met Asp Gly GlyMet Ser Ile Trp Asp Val Lys Ser Leu 115 120 125 Glu Ser Ala Leu Lys AspLeu Lys Ile Lys 130 135 222 11 PRT Homo sapiens 222 Met Ser Gly Gly LeuSer Phe Leu Leu Leu Val 1 5 10 223 23 PRT Homo sapiens 223 Leu Gly SerLeu Ser Thr Ala Pro Ser Ser Ala Leu Pro Thr Leu Gly 1 5 10 15 Ala ArgArg Thr Arg Ser Lys 20 224 66 PRT Homo sapiens 224 Met Thr Tyr Phe SerGly Leu Leu Val Ile Leu Ala Phe Ala Ala Trp 1 5 10 15 Val Ala Leu AlaGlu Gly Leu Gly Val Ala Val Tyr Ala Ala Ala Val 20 25 30 Leu Leu Gly AlaGly Cys Ala Thr Ile Leu Val Thr Ser Leu Ala Met 35 40 45 Thr Ala Asp LeuIle Gly Pro His Thr Asn Ser Gly Leu Ser Cys Thr 50 55 60 Ala Pro 65 22528 PRT Homo sapiens 225 Gly Lys Pro Thr Gly Lys Ser Leu Pro Leu Met TrpMet Ile Leu Met 1 5 10 15 Gln Pro Ile Ile Met Ile Ser Met Met Ser AsnGly 20 25 226 61 PRT Homo sapiens 226 Met Gln Gly Lys Phe Met Lys ValGln Val Tyr Arg Phe Leu Lys Tyr 1 5 10 15 Leu Leu Met Leu Leu Cys MetPhe Val Asn Arg Gly Met Ser Lys Asp 20 25 30 Ser Thr Lys Lys Pro Gly GlnGlu Lys Leu Lys Val Ser Leu Gly Ser 35 40 45 Ile Leu Asn Met Lys Ser GlnArg Pro Leu Ser Trp Cys 50 55 60 227 29 PRT Homo sapiens 227 Met Met GluArg Ser Met Met Ile Leu Leu Met Ala Ala Ser Met Thr 1 5 10 15 Met ThrSer Thr Gln Leu Trp Ser Phe Cys Cys Val His 20 25 228 18 PRT Homosapiens 228 Met Trp Tyr Gln Leu Ala Lys Glu Glu Pro Gly Val Gly Ala CysAla 1 5 10 15 Leu Asp 229 72 PRT Homo sapiens 229 Met Leu Ile Cys ArgLeu Val Leu Leu Ala Asp Pro Gly Pro Val Asn 1 5 10 15 Phe Met Val ArgLeu Phe Val Val Ile Val Met Phe Ala Trp Ser Ile 20 25 30 Val Ala Ser ThrAla Phe Leu Ala Asp Ser Gln Pro Pro Asn Arg Arg 35 40 45 Ala Leu Ala ValTyr Pro Val Phe Leu Phe Tyr Phe Val Ile Ser Trp 50 55 60 Met Ile Leu ThrPhe Thr Pro Gln 65 70 230 142 PRT Homo sapiens MISC_FEATURE (47) Xaaequals any of the L-amino acids commonly found in naturally occurringproteins 230 Met Arg Ser Leu Leu Leu Leu Ser Ala Phe Cys Leu Leu Glu AlaAla 1 5 10 15 Leu Ala Ala Glu Val Lys Lys Pro Ala Ala Ala Ala Ala ProGly Thr 20 25 30 Ala Glu Lys Leu Ser Pro Lys Ala Ala Thr Leu Ala Glu ArgXaa Arg 35 40 45 Pro Gly Leu Gln Leu Val Pro Gly His Gly Gln Gly Pro GlySer Gly 50 55 60 Glu His Pro Gly Val Thr Arg Gly Gly Gly Leu Val Ala GlyAla Arg 65 70 75 80 Val Ala Gly Arg Gln Gly Asp His Gly Val Ala Gly GlnGly Ser Ala 85 90 95 Glu Arg Arg Ala Ala Ala Arg Arg Gly Gly Ala Arg ArgPro Gly Arg 100 105 110 Ala Ala Ala Leu Thr Gln Gln Leu Xaa Gly Ala GlnArg Asp Leu Glu 115 120 125 Ala Gly Gln Pro Thr Val Arg Thr Gln Leu SerGlu Leu Arg 130 135 140 231 54 PRT Homo sapiens 231 Asp Pro Glu Ala AlaAsp Ser Gly Glu Pro Gln Asn Lys Arg Thr Pro 1 5 10 15 Asp Leu Pro GluGlu Glu Tyr Val Lys Glu Glu Ile Gln Glu Asn Glu 20 25 30 Glu Ala Val LysLys Met Leu Val Glu Ala Thr Arg Glu Phe Glu Glu 35 40 45 Val Val Val AspGlu Ser 50 232 63 PRT Homo sapiens 232 Gln Lys Leu Lys Arg Lys Ala GluGlu Asp Pro Glu Ala Ala Asp Ser 1 5 10 15 Gly Glu Pro Gln Asn Lys ArgThr Pro Asp Leu Pro Glu Glu Glu Tyr 20 25 30 Val Lys Glu Glu Ile Gln GluAsn Glu Glu Ala Val Lys Lys Met Leu 35 40 45 Val Glu Ala Thr Arg Glu PheGlu Glu Val Val Val Asp Glu Ser 50 55 60 233 113 PRT Homo sapiens 233Lys Ala Met Glu Lys Ser Ser Leu Thr Gln His Ser Trp Gln Ser Leu 1 5 1015 Lys Asp Arg Tyr Leu Lys His Leu Arg Gly Gln Glu His Lys Tyr Leu 20 2530 Leu Gly Asp Ala Pro Val Ser Pro Ser Ser Gln Lys Leu Lys Arg Lys 35 4045 Ala Glu Glu Asp Pro Glu Ala Ala Asp Ser Gly Glu Pro Gln Asn Lys 50 5560 Arg Thr Pro Asp Leu Pro Glu Glu Glu Tyr Val Lys Glu Glu Ile Gln 65 7075 80 Glu Asn Glu Glu Ala Val Lys Lys Met Leu Val Glu Ala Thr Arg Glu 8590 95 Phe Glu Glu Val Val Val Asp Glu Ser Pro Pro Asp Phe Glu Ile His100 105 110 Ile 234 148 PRT Homo sapiens 234 Leu Pro Ser Tyr Asp Glu AlaGlu Arg Thr Lys Ala Glu Ala Thr Ile 1 5 10 15 Pro Leu Val Pro Gly ArgAsp Glu Asp Phe Val Gly Arg Asp Asp Phe 20 25 30 Asp Asp Ala Asp Gln LeuArg Ile Gly Asn Asp Gly Ile Phe Met Leu 35 40 45 Thr Phe Phe Met Ala PheLeu Phe Asn Trp Ile Gly Phe Phe Leu Ser 50 55 60 Phe Cys Leu Thr Thr SerAla Ala Gly Arg Tyr Gly Ala Ile Ser Gly 65 70 75 80 Phe Gly Leu Ser LeuIle Lys Trp Ile Leu Ile Val Arg Phe Ser Thr 85 90 95 Tyr Phe Pro Gly TyrPhe Asp Gly Gln Tyr Trp Leu Trp Trp Val Phe 100 105 110 Leu Val Leu GlyPhe Leu Leu Phe Leu Arg Gly Phe Ile Asn Tyr Ala 115 120 125 Lys Val ArgLys Met Pro Glu Thr Phe Ser Asn Leu Pro Arg Thr Arg 130 135 140 Val LeuPhe Ile 145 235 24 PRT Homo sapiens 235 Ala Gly Arg Tyr Gly Ala Ile SerGly Phe Gly Leu Ser Leu Ile Lys 1 5 10 15 Trp Ile Leu Ile Val Arg PheSer 20 236 51 PRT Homo sapiens 236 Met Lys His Leu Ser Ala Trp Asn PheThr Lys Leu Thr Phe Leu Gln 1 5 10 15 Leu Trp Glu Ile Phe Glu Gly SerVal Glu Asn Cys Gln Thr Leu Thr 20 25 30 Ser Tyr Ser Lys Leu Gln Ile LysTyr Thr Phe Ser Arg Gly Ser Thr 35 40 45 Phe Tyr Ile 50 237 213 PRT Homosapiens 237 Phe Ser Ser Asp Phe Arg Thr Ser Pro Trp Glu Ser Arg Arg ValGlu 1 5 10 15 Ser Lys Ala Thr Ser Ala Arg Cys Gly Leu Trp Gly Ser GlyPro Arg 20 25 30 Arg Arg Pro Ala Ser Gly Met Phe Arg Gly Leu Ser Ser TrpLeu Gly 35 40 45 Leu Gln Gln Pro Val Ala Gly Gly Gly Gln Pro Asn Gly AspAla Pro 50 55 60 Pro Glu Gln Pro Ser Glu Thr Val Ala Glu Ser Ala Glu GluGlu Leu 65 70 75 80 Gln Gln Ala Gly Asp Gln Glu Leu Leu His Gln Ala LysAsp Phe Gly 85 90 95 Asn Tyr Leu Phe Asn Phe Ala Ser Ala Ala Thr Lys LysIle Thr Glu 100 105 110 Ser Val Ala Glu Thr Ala Gln Thr Ile Lys Lys SerVal Glu Glu Gly 115 120 125 Lys Ile Asp Gly Ile Ile Asp Lys Thr Ile IleGly Asp Phe Gln Lys 130 135 140 Glu Gln Lys Lys Phe Val Glu Glu Gln HisThr Lys Lys Ser Glu Ala 145 150 155 160 Ala Val Pro Pro Trp Val Asp ThrAsn Asp Glu Glu Thr Ile Gln Gln 165 170 175 Gln Ile Leu Ala Leu Ser AlaAsp Lys Arg Asn Phe Leu Arg Asp Pro 180 185 190 Pro Ala Gly Val Gln PheAsn Phe Asp Phe Asp Gln Met Tyr Pro Val 195 200 205 Ala Leu Val Met Leu210 238 49 PRT Homo sapiens 238 Met Arg Phe Ala Leu Val Pro Lys Leu ValLys Glu Glu Val Phe Trp 1 5 10 15 Arg Asn Tyr Phe Tyr Arg Val Ser LeuIle Lys Gln Ser Ala Gln Leu 20 25 30 Thr Ala Leu Ala Ala Gln Gln Gln AlaAla Gly Lys Gly Gly Glu Glu 35 40 45 Gln 239 76 PRT Homo sapiens 239 SerThr Ser Pro Gly Val Ser Glu Phe Val Ser Asp Ala Phe Asp Ala 1 5 10 15Cys Asn Leu Asn Gln Glu Asp Leu Arg Lys Glu Met Glu Gln Leu Val 20 25 30Leu Asp Lys Lys Gln Glu Glu Thr Ala Val Leu Glu Glu Asp Ser Ala 35 40 45Asp Trp Glu Lys Glu Leu Gln Gln Glu Leu Gln Glu Tyr Glu Val Val 50 55 60Thr Glu Ser Glu Lys Arg Asp Glu Asn Trp Asp Lys 65 70 75 240 62 PRT Homosapiens 240 Ser Pro Trp Glu Ser Arg Arg Val Glu Ser Lys Ala Thr Ser AlaArg 1 5 10 15 Cys Gly Leu Trp Gly Ser Gly Pro Arg Arg Arg Pro Ala SerGly Met 20 25 30 Phe Arg Gly Leu Ser Ser Trp Leu Gly Leu Gln Gln Pro ValAla Gly 35 40 45 Gly Gly Gln Pro Asn Gly Asp Ala Pro Pro Glu Gln Pro Ser50 55 60 241 65 PRT Homo sapiens 241 Pro Val Ala Gly Gly Gly Gln Pro AsnGly Asp Ala Pro Pro Glu Gln 1 5 10 15 Pro Ser Glu Thr Val Ala Glu SerAla Glu Glu Glu Leu Gln Gln Ala 20 25 30 Gly Asp Gln Glu Leu Leu His GlnAla Lys Asp Phe Gly Asn Tyr Leu 35 40 45 Phe Asn Phe Ala Ser Ala Ala ThrLys Lys Ile Thr Glu Ser Val Ala 50 55 60 Glu 65 242 72 PRT Homo sapiens242 Phe Gln Lys Glu Gln Lys Lys Phe Val Glu Glu Gln His Thr Lys Lys 1 510 15 Ser Glu Ala Ala Val Pro Pro Trp Val Asp Thr Asn Asp Glu Glu Thr 2025 30 Ile Gln Gln Gln Ile Leu Ala Leu Ser Ala Asp Lys Arg Asn Phe Leu 3540 45 Arg Asp Pro Pro Ala Gly Val Gln Phe Asn Phe Asp Phe Asp Gln Met 5055 60 Tyr Pro Val Ala Leu Val Met Leu 65 70 243 28 PRT Homo sapiens 243Pro Phe Ile Cys Val Ala Arg Asn Pro Val Ser Arg Asn Phe Ser Ser 1 5 1015 Pro Ile Leu Ala Arg Lys Leu Cys Glu Gly Ala Ala 20 25 244 33 PRT Homosapiens 244 Lys Glu Asp Pro Ala Asn Thr Val Tyr Ser Thr Val Glu Ile ProLys 1 5 10 15 Lys Met Glu Asn Pro His Ser Leu Leu Thr Met Pro Asp ThrPro Arg 20 25 30 Leu 245 227 PRT Homo sapiens 245 Ala Ser Ala Val LeuLeu Asp Leu Pro Asn Ser Gly Gly Glu Ala Gln 1 5 10 15 Ala Lys Lys LeuGly Asn Asn Cys Val Phe Ala Pro Ala Asp Val Thr 20 25 30 Ser Glu Lys AspVal Gln Thr Ala Leu Ala Leu Ala Lys Gly Lys Phe 35 40 45 Gly Arg Val AspVal Ala Val Asn Cys Ala Gly Ile Ala Val Ala Ser 50 55 60 Lys Thr Tyr AsnLeu Lys Lys Gly Gln Thr His Thr Leu Glu Asp Phe 65 70 75 80 Gln Arg ValLeu Asp Val Asn Leu Met Gly Thr Phe Asn Val Ile Arg 85 90 95 Leu Val AlaGly Glu Met Gly Gln Asn Glu Pro Asp Gln Gly Gly Gln 100 105 110 Arg GlyVal Ile Ile Asn Thr Ala Ser Val Ala Ala Phe Glu Gly Gln 115 120 125 ValGly Gln Ala Ala Tyr Ser Ala Ser Lys Gly Gly Ile Val Gly Met 130 135 140Thr Leu Pro Ile Ala Arg Asp Leu Ala Pro Ile Gly Ile Arg Val Met 145 150155 160 Thr Ile Ala Pro Gly Leu Phe Gly Thr Pro Leu Leu Thr Ser Leu Pro165 170 175 Glu Lys Val Cys Asn Phe Leu Ala Ser Gln Val Pro Phe Pro SerArg 180 185 190 Leu Gly Asp Pro Ala Glu Tyr Ala His Leu Val Gln Ala IleIle Glu 195 200 205 Asn Pro Phe Leu Asn Gly Glu Val Ile Arg Leu Asp GlyAla Ile Arg 210 215 220 Met Gln Pro 225 246 29 PRT Homo sapiens 246 SerVal Ala Ala Phe Glu Gly Gln Val Gly Gln Ala Ala Tyr Ser Ala 1 5 10 15Ser Lys Gly Gly Ile Val Gly Met Thr Leu Pro Ile Ala 20 25 247 29 PRTHomo sapiens 247 Ser Val Ala Ala Phe Glu Gly Gln Val Gly Gln Ala Ala TyrSer Ala 1 5 10 15 Ser Lys Gly Gly Ile Val Gly Met Thr Leu Pro Ile Ala 2025 248 22 PRT Homo sapiens 248 His Pro Ile Glu Trp Ala Ile Asn Ala AlaThr Leu Ser Gln Phe Tyr 1 5 10 15 Ile Asn Lys Leu Cys Phe 20 249 22 PRTHomo sapiens 249 Cys Trp Ile Lys Tyr Cys Leu Thr Leu Met Gln Asn Ala GlnLeu Ser 1 5 10 15 Met Gln Asp Asn Ile Gly 20 250 25 PRT Homo sapiens 250Lys Val Ser Tyr Leu Arg Pro Leu Asp Phe Glu Glu Ala Arg Glu Leu 1 5 1015 Phe Leu Leu Gly Gln His Tyr Val Phe 20 25 251 25 PRT Homo sapiensMISC_FEATURE (11) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 251 Met Glu Arg Arg Cys Lys Met His Lys ArgXaa Ile Ala Met Leu Glu 1 5 10 15 Pro Leu Thr Val Asp Leu Asn Pro Gln 2025 252 23 PRT Homo sapiens 252 Ser His Ile Val Lys Lys Ile Asn Asn LeuAsn Lys Ser Ala Leu Lys 1 5 10 15 Tyr Tyr Gln Leu Phe Leu Asp 20 253 64PRT Homo sapiens 253 Phe Thr His Leu Ser Thr Cys Leu Leu Ser Leu Leu LeuVal Arg Met 1 5 10 15 Ser Gly Phe Leu Leu Leu Ala Arg Ala Ser Pro SerIle Cys Ala Leu 20 25 30 Asp Ser Ser Cys Phe Val Gln Glu Tyr Cys Ser SerTyr Ser Ser Ser 35 40 45 Cys Phe Leu His Gln His Phe Pro Ser Leu Leu AspHis Leu Cys Gln 50 55 60 254 23 PRT Homo sapiens 254 Phe Leu Leu Leu AlaArg Ala Ser Pro Ser Ile Cys Ala Leu Asp Ser 1 5 10 15 Ser Cys Phe ValGln Glu Tyr 20 255 53 PRT Homo sapiens 255 Pro Asp Gly Arg Val Thr AsnIle Pro Gln Gly Met Val Thr Asp Gln 1 5 10 15 Phe Gly Met Ile Gly LeuLeu Thr Phe Ile Arg Ala Ala Glu Thr Asp 20 25 30 Pro Gly Met Val His LeuAla Leu Gly Ser Asp Leu Thr Thr Leu Gly 35 40 45 Leu Asn Leu Asn Ser 50256 41 PRT Homo sapiens 256 Glu Asp Leu Leu Phe Tyr Leu Tyr Tyr Met AsnGly Gly Asp Val Leu 1 5 10 15 Gln Leu Leu Ala Ala Val Glu Leu Phe AsnArg Asp Trp Arg Tyr His 20 25 30 Lys Glu Glu Arg Val Trp Ile Thr Arg 3540 257 24 PRT Homo sapiens 257 Val His Leu Ala Leu Gly Ser Asp Leu ThrThr Leu Gly Leu Asn Leu 1 5 10 15 Asn Ser Pro Glu Asn Leu Tyr Pro 20 25841 PRT Homo sapiens 258 Glu Asp Leu Leu Phe Tyr Leu Tyr Tyr Met Asn GlyGly Asp Val Leu 1 5 10 15 Gln Leu Leu Ala Ala Val Glu Leu Phe Asn ArgAsp Trp Arg Tyr His 20 25 30 Lys Glu Glu Arg Val Trp Ile Thr Arg 35 40259 11 PRT Homo sapiens 259 His Asn Glu Asp Phe Pro Ala Leu Pro Gly Ser1 5 10 260 75 PRT Homo sapiens 260 Gly Arg Ile Ile Asp Thr Ser Leu ThrArg Asp Pro Leu Val Ile Glu 1 5 10 15 Leu Gly Gln Lys Gln Val Ile ProGly Leu Glu Gln Ser Leu Leu Asp 20 25 30 Met Cys Val Gly Glu Lys Arg ArgAla Ile Ile Pro Ser His Leu Ala 35 40 45 Tyr Gly Lys Arg Gly Phe Pro ProSer Val Pro Ala Asp Ala Val Val 50 55 60 Gln Tyr Asp Val Glu Leu Ile AlaLeu Ile Arg 65 70 75 261 16 PRT Homo sapiens 261 Ile His Tyr Thr Gly SerLeu Val Asp Gly Arg Ile Ile Asp Thr Ser 1 5 10 15 262 20 PRT Homosapiens 262 Cys Glu Ser Pro Glu Ser Pro Ala Gln Pro Ser Gly Ser Ser LeuPro 1 5 10 15 Ala Trp Tyr His 20 263 95 PRT Homo sapiens 263 Glu Glu AlaGly Ala Gly Arg Arg Cys Ser His Gly Gly Ala Arg Pro 1 5 10 15 Ala GlyLeu Gly Asn Glu Gly Leu Gly Leu Gly Gly Asp Pro Asp His 20 25 30 Thr AspThr Gly Ser Arg Ser Lys Gln Arg Ile Asn Asn Trp Lys Glu 35 40 45 Ser LysHis Lys Val Ile Met Ala Ser Ala Ser Ala Arg Gly Asn Gln 50 55 60 Asp LysAsp Ala His Phe Pro Pro Pro Ser Lys Gln Ser Leu Leu Phe 65 70 75 80 CysPro Lys Ser Lys Leu His Ile His Arg Ala Glu Ile Ser Lys 85 90 95 264 23PRT Homo sapiens 264 Ser Lys Gln Arg Ile Asn Asn Trp Lys Glu Ser Lys HisLys Val Ile 1 5 10 15 Met Ala Ser Ala Ser Ala Arg 20 265 32 PRT Homosapiens MISC_FEATURE (20) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 265 Leu Phe His Trp Ala Cys LeuAsn Glu Arg Ala Ala Gln Leu Pro Arg 1 5 10 15 Asn Thr Ala Xaa Ala GlyTyr Gln Cys Pro Ser Cys Asn Gly Pro Ser 20 25 30 266 185 PRT Homosapiens 266 Phe Tyr Ile Tyr Tyr Arg Pro Thr Asp Ser Asp Asn Asp Ser AspTyr 1 5 10 15 Lys Lys Asp Met Val Glu Gly Asp Lys Tyr Trp His Ser IleSer His 20 25 30 Leu Gln Pro Glu Thr Ser Tyr Asp Ile Lys Met Gln Cys PheAsn Glu 35 40 45 Gly Gly Glu Ser Glu Phe Ser Asn Val Met Ile Cys Glu ThrLys Ala 50 55 60 Arg Lys Ser Ser Gly Gln Pro Gly Arg Leu Pro Pro Pro ThrLeu Ala 65 70 75 80 Pro Pro Gln Pro Pro Leu Pro Glu Thr Ile Glu Arg ProVal Gly Thr 85 90 95 Gly Ala Met Val Ala Arg Ser Ser Asp Leu Pro Tyr LeuIle Val Gly 100 105 110 Val Val Leu Gly Ser Ile Val Leu Ile Ile Val ThrPhe Ile Pro Phe 115 120 125 Cys Leu Trp Arg Ala Trp Ser Lys Gln Lys HisThr Thr Asp Leu Gly 130 135 140 Phe Pro Arg Ser Ala Leu Pro Pro Ser CysPro Tyr Thr Met Val Pro 145 150 155 160 Leu Gly Gly Leu Pro Gly His GlnAla Val Asp Ser Pro Thr Ser Val 165 170 175 Ala Ser Val Asp Gly Pro ValLeu Met 180 185 267 66 PRT Homo sapiens 267 Tyr Ile Tyr Tyr Arg Pro ThrAsp Ser Asp Asn Asp Ser Asp Tyr Lys 1 5 10 15 Lys Asp Met Val Glu GlyAsp Lys Tyr Trp His Ser Ile Ser His Leu 20 25 30 Gln Pro Glu Thr Ser TyrAsp Ile Lys Met Gln Cys Phe Asn Glu Gly 35 40 45 Gly Glu Ser Glu Phe SerAsn Val Met Ile Cys Glu Thr Lys Ala Arg 50 55 60 Lys Ser 65 268 30 PRTHomo sapiens 268 Asn Val Arg Ala Leu Leu His Arg Met Pro Glu Pro Pro LysIle Asn 1 5 10 15 Thr Ala Lys Phe Asn Asn Asn Lys Arg Lys Asn Leu SerLeu 20 25 30 269 185 PRT Homo sapiens 269 Asn Thr Asn Gln Arg Glu AlaLeu Gln Tyr Ala Lys Asn Phe Gln Pro 1 5 10 15 Phe Ala Leu Asn His GlnLys Asp Ile Gln Val Leu Met Gly Ser Leu 20 25 30 Val Tyr Leu Arg Gln GlyIle Glu Asn Ser Pro Tyr Val His Leu Leu 35 40 45 Asp Ala Asn Gln Trp AlaAsp Ile Cys Asp Ile Phe Thr Arg Asp Ala 50 55 60 Cys Ala Leu Leu Gly LeuSer Val Glu Ser Pro Leu Ser Val Ser Phe 65 70 75 80 Ser Ala Gly Cys ValAla Leu Pro Ala Leu Ile Asn Ile Lys Ala Val 85 90 95 Ile Glu Gln Arg GlnCys Thr Gly Val Trp Asn Gln Lys Asp Glu Leu 100 105 110 Pro Ile Glu ValAsp Leu Gly Lys Lys Cys Trp Tyr His Ser Ile Phe 115 120 125 Ala Cys ProIle Leu Arg Gln Gln Thr Thr Asp Asn Asn Pro Pro Met 130 135 140 Lys LeuVal Cys Gly His Ile Ile Ser Arg Asp Ala Leu Asn Lys Met 145 150 155 160Phe Asn Gly Ser Lys Leu Lys Cys Pro Tyr Cys Pro Met Glu Gln Ser 165 170175 Pro Gly Asp Ala Lys Gln Ile Phe Phe 180 185 270 65 PRT Homo sapiens270 Ser Tyr Leu Ser Ala Cys Phe Ala Gly Cys Asn Ser Thr Asn Leu Thr 1 510 15 Gly Cys Ala Cys Leu Thr Thr Val Pro Ala Glu Asn Ala Thr Val Val 2025 30 Pro Gly Lys Cys Pro Ser Pro Gly Cys Gln Glu Ala Phe Leu Thr Phe 3540 45 Leu Cys Val Met Cys Ile Cys Ser Leu Ile Gly Ala Met Ala Arg His 5055 60 Pro 65 271 84 PRT Homo sapiens 271 Pro Ser Val Ile Ile Leu Ile ArgThr Val Ser Pro Glu Leu Lys Ser 1 5 10 15 Tyr Ala Leu Gly Val Leu PheLeu Leu Leu Arg Leu Leu Gly Phe Ile 20 25 30 Pro Pro Pro Leu Ile Phe GlyAla Gly Ile Asp Ser Thr Cys Leu Phe 35 40 45 Trp Ser Thr Phe Cys Gly GluGln Gly Ala Cys Val Leu Tyr Asp Asn 50 55 60 Val Val Tyr Arg Tyr Leu TyrVal Ser Ile Ala Ile Ala Leu Lys Ser 65 70 75 80 Phe Ala Phe Ile 272 182PRT Homo sapiens MISC_FEATURE (29) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 272 Gln Ser Leu Phe ThrArg Phe Val Arg Val Gly Val Pro Thr Val Asp 1 5 10 15 Leu Asp Ala GlnGly Arg Ala Arg Ala Ser Leu Cys Xaa Xaa Tyr Asn 20 25 30 Trp Arg Tyr LysAsn Leu Gly Asn Leu Pro His Val Gln Leu Leu Pro 35 40 45 Glu Phe Ser ThrAla Asn Ala Gly Leu Leu Tyr Asp Phe Gln Leu Ile 50 55 60 Asn Val Glu AspPhe Gln Gly Val Gly Glu Ser Glu Pro Asn Pro Tyr 65 70 75 80 Phe Tyr GlnAsn Leu Gly Glu Ala Glu Tyr Val Val Ala Leu Phe Met 85 90 95 Tyr Met CysLeu Leu Gly Tyr Pro Ala Asp Lys Ile Ser Ile Leu Thr 100 105 110 Thr TyrAsn Gly Gln Lys His Leu Ile Arg Asp Ile Ile Asn Arg Arg 115 120 125 CysGly Asn Asn Pro Leu Ile Gly Arg Pro Asn Lys Val Thr Thr Val 130 135 140Asp Arg Phe Gln Gly Gln Gln Asn Asp Tyr Ile Leu Leu Ser Leu Val 145 150155 160 Arg Thr Arg Ala Val Gly His Leu Arg Asp Val Arg Arg Leu Val Val165 170 175 Ala Met Ser Arg Ala Arg 180 273 77 PRT Homo sapiens 273 LeuVal Lys Glu Ala Lys Ile Ile Ala Met Thr Cys Thr His Ala Ala 1 5 10 15Leu Lys Arg His Asp Leu Val Lys Leu Gly Phe Lys Tyr Asp Asn Ile 20 25 30Leu Met Glu Glu Ala Ala Gln Ile Leu Glu Ile Glu Thr Phe Ile Pro 35 40 45Leu Leu Leu Gln Asn Pro Gln Asp Gly Phe Ser Arg Leu Lys Arg Trp 50 55 60Ile Met Ile Gly Asp His His Gln Leu Pro Pro Val Ile 65 70 75 274 125 PRTHomo sapiens MISC_FEATURE (16) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 274 Asp Thr Tyr Pro AsnGlu Glu Lys Gln Gln Glu Arg Val Phe Pro Xaa 1 5 10 15 Xaa Ser Ala MetVal Asn Asn Gly Ser Leu Ser Tyr Asp His Glu Arg 20 25 30 Asp Gly Arg ProThr Glu Leu Gly Gly Cys Xaa Ala Ile Val Arg Asn 35 40 45 Leu His Tyr AspThr Phe Leu Val Ile Arg Tyr Val Lys Arg His Leu 50 55 60 Thr Ile Met MetAsp Ile Asp Gly Lys His Glu Trp Arg Asp Cys Ile 65 70 75 80 Glu Val ProGly Val Arg Leu Pro Arg Gly Tyr Tyr Phe Gly Thr Ser 85 90 95 Ser Ile ThrGly Asp Leu Ser Asp Asn His Asp Val Ile Ser Leu Lys 100 105 110 Leu PheGlu Leu Thr Val Glu Arg Thr Pro Glu Glu Glu 115 120 125 275 85 PRT Homosapiens 275 Leu Lys Arg Glu His Ser Leu Ser Lys Pro Tyr Gln Gly Val GlyThr 1 5 10 15 Gly Ser Ser Ser Leu Trp Asn Leu Met Gly Asn Ala Met ValMet Thr 20 25 30 Gln Tyr Ile Arg Leu Thr Pro Asp Met Gln Ser Lys Gln GlyAla Leu 35 40 45 Trp Asn Arg Val Pro Cys Phe Leu Arg Asp Trp Glu Leu GlnVal His 50 55 60 Phe Lys Ile His Gly Gln Gly Lys Lys Asn Leu His Gly AspGly Leu 65 70 75 80 Ala Ile Trp Tyr Thr 85 276 32 PRT Homo sapiens 276Pro Gly Thr Leu Gln Cys Ser Ala Leu His His Asp Pro Gly Cys Ala 1 5 1015 Asn Cys Ser Arg Phe Cys Arg Asp Cys Ser Pro Pro Ala Cys Gln Cys 20 2530 277 27 PRT Homo sapiens MISC_FEATURE (8) Xaa equals any of theL-amino acids commonly found in naturally occurring proteins 277 Phe LeuTyr Asp Val Leu Met Xaa His Glu Ala Val Met Arg Thr His 1 5 10 15 GlnIle Gln Leu Pro Asp Pro Glu Phe Pro Ser 20 25 278 92 PRT Homo sapiensMISC_FEATURE (4) Xaa equals any of the L-amino acids commonly found innaturally occurring proteins 278 Pro Ala Asp Xaa Lys Pro Val Val Ser ThrGlu Ala Pro Pro Ile Ile 1 5 10 15 Phe Ala Thr Pro Thr Lys Leu Thr SerAsp Ser Thr Val Tyr Asp Tyr 20 25 30 Ala Gly Lys Asn Lys Val Pro Glu LeuGln Lys Phe Phe Gln Lys Ala 35 40 45 Asp Gly Val Pro Val Tyr Leu Lys ArgGly Leu Pro Asp Gln Met Leu 50 55 60 Tyr Arg Thr Thr Met Ala Leu Thr ValGly Gly Thr Ile Tyr Cys Leu 65 70 75 80 Ile Ala Leu Tyr Met Ala Ser GlnPro Lys Asn Lys 85 90 279 63 PRT Homo sapiens MISC_FEATURE (45) Xaaequals any of the L-amino acids commonly found in naturally occurringproteins 279 Ser Phe Ser Gly Ala Val Ala Leu Ala Ala Asp Ala Gly Ser ArgThr 1 5 10 15 Leu Gly Val Met Tyr Tyr Lys Phe Ser Gly Phe Thr Gln LysLeu Ala 20 25 30 Gly Ala Trp Ala Ser Glu Ala Tyr Ser Pro Gln Ile Xaa SerLeu Trp 35 40 45 Phe Pro Gln Lys His His Leu Ser Tyr Leu Pro His Gln LeuAsn 50 55 60 280 6 PRT Homo sapiens 280 Gly Trp Tyr Trp Cys Gly 1 5 281129 PRT Homo sapiens 281 Met Lys Val Gly Ala Arg Ile Arg Val Lys Met SerVal Asn Lys Ala 1 5 10 15 His Pro Val Val Ser Thr His Trp Arg Trp ProAla Glu Trp Pro Gln 20 25 30 Met Phe Leu His Leu Ala Gln Glu Pro Arg ThrGlu Val Lys Ser Arg 35 40 45 Pro Leu Gly Leu Ala Gly Phe Ile Arg Gln AspSer Lys Thr Arg Lys 50 55 60 Pro Leu Glu Gln Glu Thr Ile Met Ser Ala AlaAsp Thr Ala Leu Trp 65 70 75 80 Pro Tyr Gly His Gly Asn Arg Glu His GlnGlu Asn Glu Leu Gln Lys 85 90 95 Tyr Leu Gln Tyr Lys Asp Met His Leu LeuAsp Ser Gly Gln Ser Leu 100 105 110 Gly His Thr His Thr Leu Gln Gly SerHis Asn Leu Thr Ala Leu Asn 115 120 125 Ile 282 49 PRT Homo sapiens 282Ser Leu His Lys Asn Ser Val Ser Gln Ile Ser Val Leu Ser Gly Gly 1 5 1015 Lys Ala Lys Cys Ser Gln Phe Cys Thr Thr Gly Met Asp Gly Gly Met 20 2530 Ser Ile Trp Asp Val Lys Ser Leu Glu Ser Ala Leu Lys Asp Leu Lys 35 4045 Ile 283 21 PRT Homo sapiens 283 Glu Ala Ser Lys Ser Ser His Ala GlyLeu Asp Leu Phe Ser Val Ala 1 5 10 15 Ala Cys His Arg Phe 20 284 21 PRTHomo sapiens 284 Tyr Met Gly Lys Gly Ser Met Thr Gly Leu Ala Leu Lys HisMet Phe 1 5 10 15 Glu Arg Ser Phe Thr 20 285 27 PRT Homo sapiens 285 ValThr Gly Ile Ile Asp Ser Leu Thr Ile Ser Pro Lys Ala Ala Arg 1 5 10 15Val Gly Leu Leu Gln Tyr Ser Thr Gln Val His 20 25 286 24 PRT Homosapiens 286 Thr Glu Phe Thr Leu Arg Asn Phe Asn Ser Ala Lys Asp Met LysLys 1 5 10 15 Ala Val Ala His Met Lys Tyr Met 20 287 27 PRT Homo sapiens287 Gly Lys Gly Ser Met Thr Gly Leu Ala Leu Lys His Met Phe Glu Arg 1 510 15 Ser Phe Thr Gln Gly Glu Gly Ala Arg Pro Phe 20 25 288 44 PRT Homosapiens 288 Ser Thr Arg Val Pro Arg Ala Ala Ile Val Phe Thr Asp Gly ArgAla 1 5 10 15 Gln Asp Asp Val Ser Glu Trp Ala Ser Lys Ala Lys Ala AsnGly Ile 20 25 30 Thr Met Tyr Ala Val Gly Val Gly Lys Ala Ile Glu 35 40289 42 PRT Homo sapiens 289 Glu Glu Leu Gln Glu Ile Ala Ser Glu Pro ThrAsn Lys His Leu Phe 1 5 10 15 Tyr Ala Glu Asp Phe Ser Thr Met Asp GluIle Ser Glu Lys Leu Lys 20 25 30 Lys Gly Ile Cys Glu Ala Leu Glu Asp Ser35 40 290 11 PRT Homo sapiens 290 Thr Gln Arg Leu Glu Glu Met Thr GlnArg Met 1 5 10 291 10 PRT Homo sapiens 291 Pro Gln Gly Cys Pro Glu GlnPro Leu His 1 5 10 292 33 PRT Homo sapiens 292 Arg Cys Lys Lys Cys ThrGlu Gly Pro Ile Asp Leu Val Phe Val Ile 1 5 10 15 Asp Gly Ser Lys SerLeu Gly Glu Glu Asn Phe Glu Val Val Lys Gln 20 25 30 Phe 293 193 PRTHomo sapiens MISC_FEATURE (35) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 293 Gly Trp Glu Thr LeuPro Lys Lys Asp Val Cys Lys Ser Thr His His 1 5 10 15 Gly Cys Glu HisIle Cys Val Asn Asn Gly Asn Ser Tyr Ile Cys Lys 20 25 30 Cys Ser Xaa GlyPhe Val Leu Ala Glu Asp Gly Arg Arg Cys Lys Lys 35 40 45 Cys Thr Glu GlyPro Ile Asp Leu Val Phe Val Ile Asp Gly Ser Lys 50 55 60 Ser Leu Gly GluGlu Asn Phe Glu Val Val Lys Gln Phe Val Thr Gly 65 70 75 80 Ile Ile AspSer Leu Thr Ile Ser Pro Lys Ala Ala Arg Val Gly Leu 85 90 95 Leu Gln TyrSer Thr Gln Val His Thr Glu Phe Thr Leu Arg Asn Phe 100 105 110 Asn SerAla Lys Asp Met Lys Lys Ala Val Ala His Met Lys Tyr Met 115 120 125 GlyLys Gly Ser Met Thr Gly Leu Ala Leu Lys His Met Phe Glu Arg 130 135 140Ser Phe Thr Gln Gly Glu Gly Ala Arg Pro Phe Pro Gln Gly Cys Pro 145 150155 160 Glu Gln Pro Leu Cys Ser Pro Thr Asp Gly Leu Arg Met Thr Ser Pro165 170 175 Ser Gly Pro Val Lys Pro Arg Pro Met Val Ser Leu Cys Met LeuLeu 180 185 190 Gly 294 193 PRT Homo sapiens 294 Lys Phe Tyr Pro Arg ArgArg Gly Gln Ala Leu Ser Thr Arg Val Pro 1 5 10 15 Arg Ala Ala Ile ValPhe Thr Asp Gly Arg Ala Gln Asp Asp Val Ser 20 25 30 Glu Trp Ala Ser LysAla Lys Ala Asn Gly Ile Thr Met Tyr Ala Val 35 40 45 Gly Val Gly Lys AlaIle Glu Glu Glu Leu Gln Glu Ile Ala Ser Glu 50 55 60 Pro Thr Asn Lys HisLeu Phe Tyr Ala Glu Asp Phe Ser Thr Met Asp 65 70 75 80 Glu Ile Ser GluLys Leu Lys Lys Gly Ile Cys Glu Ala Leu Glu Asp 85 90 95 Ser Asp Gly ArgGln Asp Ser Pro Ala Gly Glu Leu Pro Lys Thr Val 100 105 110 Gln Gln ProThr Val Gln His Arg Tyr Leu Phe Glu Glu Asp Asn Leu 115 120 125 Leu ArgSer Thr Gln Lys Leu Ser His Ser Thr Lys Pro Ser Gly Ser 130 135 140 ProLeu Glu Glu Lys His Asp Gln Cys Lys Cys Glu Asn Leu Ile Met 145 150 155160 Phe Gln Asn Leu Ala Asn Glu Glu Val Arg Lys Leu Thr Gln Arg Leu 165170 175 Glu Glu Met Thr Gln Arg Met Glu Ala Leu Glu Asn Arg Leu Arg Tyr180 185 190 Arg 295 60 PRT Homo sapiens 295 Met Ala Ala Leu Leu Leu ArgHis Val Gly Arg His Cys Leu Arg Ala 1 5 10 15 His Phe Ser Pro Gln LeuCys Ile Arg Asn Ala Val Pro Leu Gly Thr 20 25 30 Thr Ala Lys Glu Glu MetGlu Arg Phe Trp Asn Lys Asn Ile Gly Ser 35 40 45 Asn Arg Pro Leu Ser ProHis Ile Thr Ile Tyr Ser 50 55 60 296 32 PRT Homo sapiens 296 Val Phe ProLeu Met Tyr His Thr Trp Asn Gly Ile Arg His Leu Met 1 5 10 15 Trp AspLeu Gly Lys Gly Leu Lys Ile Pro Gln Leu Tyr Gln Ser Gly 20 25 30 297 17PRT Homo sapiens 297 Met Ala Ala Leu Leu Leu Arg His Val Gly Arg His CysLeu Arg Ala 1 5 10 15 His 298 18 PRT Homo sapiens 298 Val Lys Ser LeuCys Leu Gly Pro Ala Leu Ile His Thr Ala Lys Phe 1 5 10 15 Ala Leu 299 23PRT Homo sapiens 299 Val Phe Pro Leu Met Tyr His Thr Trp Asn Gly Ile ArgHis Leu Met 1 5 10 15 Trp Asp Leu Gly Lys Gly Leu 20 300 22 PRT Homosapiens 300 Arg Val Trp Asp Val Arg Pro Phe Ala Pro Lys Glu Arg Cys ValLys 1 5 10 15 Ile Phe Gln Gly Asn Val 20 301 30 PRT Homo sapiens 301 HisAsn Phe Glu Lys Asn Leu Leu Arg Cys Ser Trp Ser Pro Asp Gly 1 5 10 15Ser Lys Ile Ala Ala Gly Ser Ala Asp Arg Phe Val Tyr Val 20 25 30 302 30PRT Homo sapiens 302 Trp Asp Thr Thr Ser Arg Arg Ile Leu Tyr Lys Leu ProGly His Ala 1 5 10 15 Gly Ser Ile Asn Glu Val Ala Phe His Pro Asp GluPro Ile 20 25 30 303 141 PRT Homo sapiens 303 Tyr Gln Gly Leu Gly LeuArg Gln Asn Lys Leu Thr Tyr Thr Met Arg 1 5 10 15 Gly His Ala Asp SerVal Thr Gly Leu Ser Leu Ser Ser Glu Gly Ser 20 25 30 Tyr Leu Leu Ser AsnAla Met Asp Asn Thr Val Arg Val Trp Asp Val 35 40 45 Arg Pro Phe Ala ProLys Glu Arg Cys Val Lys Ile Phe Gln Gly Asn 50 55 60 Val His Asn Phe GluLys Asn Leu Leu Arg Cys Ser Trp Ser Pro Asp 65 70 75 80 Gly Ser Lys IleAla Ala Gly Ser Ala Asp Arg Phe Val Tyr Val Trp 85 90 95 Asp Thr Thr SerArg Arg Ile Leu Tyr Lys Leu Pro Gly His Ala Gly 100 105 110 Ser Ile AsnGlu Val Ala Phe His Pro Asp Glu Pro Ile Ile Ile Ser 115 120 125 Ala SerSer Asp Lys Arg Leu Tyr Met Gly Glu Ile Gln 130 135 140 304 45 PRT Homosapiens 304 Arg Lys Lys Ala Ala Ile Gln Thr Phe Gln Asn Thr Tyr Gln ValLeu 1 5 10 15 Ala Val Thr Phe Asn Asp Thr Ser Asp Gln Ile Ile Ser GlyGly Ile 20 25 30 Asp Asn Asp Ile Lys Val Trp Asp Cys Ala Arg Thr Ser 3540 45 305 20 PRT Homo sapiens 305 Val Arg Gly Arg Thr Val Leu Arg ProGly Leu Asp Ala Glu Pro Glu 1 5 10 15 Leu Ser Pro Glu 20 306 19 PRT Homosapiens 306 Glu Gln Arg Val Leu Glu Arg Lys Leu Lys Lys Glu Arg Lys LysGlu 1 5 10 15 Glu Arg Gln 307 13 PRT Homo sapiens 307 Arg Leu Arg GluAla Gly Leu Val Ala Gln His Pro Pro 1 5 10 308 17 PRT Homo sapiens 308Gly Arg Ile Pro Ala Pro Ala Pro Ser Val Pro Ala Gly Pro Asp Ser 1 5 1015 Arg 309 61 PRT Homo sapiens 309 Ala Arg Arg Ser Gly Ala Glu Leu AlaTrp Asp Tyr Leu Cys Arg Trp 1 5 10 15 Ala Gln Lys His Lys Asn Trp ArgPhe Gln Lys Thr Arg Gln Thr Trp 20 25 30 Leu Leu Leu His Met Tyr Asp SerAsp Lys Val Pro Asp Glu His Phe 35 40 45 Ser Thr Leu Leu Ala Tyr Leu GluGly Leu Gln Gly Arg 50 55 60 310 42 PRT Homo sapiens 310 Thr Gly Cys ValLeu Val Leu Ser Arg Asn Phe Val Gln Tyr Ala Cys 1 5 10 15 Phe Gly LeuPhe Gly Ile Ile Ala Leu Gln Thr Ile Ala Tyr Ser Ile 20 25 30 Leu Trp AspLeu Lys Phe Leu Met Arg Asn 35 40 311 55 PRT Homo sapiens 311 Ser ArgSer Glu Gly Lys Ser Met Phe Ala Gly Val Pro Thr Met Arg 1 5 10 15 GluSer Ser Pro Lys Gln Tyr Met Gln Leu Gly Gly Arg Val Leu Leu 20 25 30 ValLeu Met Phe Met Thr Leu Leu His Phe Asp Ala Ser Phe Phe Ser 35 40 45 IleVal Gln Asn Ile Val Gly 50 55 312 60 PRT Homo sapiens 312 Gly Thr AlaGlu Asp Phe Ala Asp Gln Phe Leu Arg Val Thr Lys Gln 1 5 10 15 Tyr LeuPro His Val Ala Arg Leu Cys Leu Ile Ser Thr Phe Leu Glu 20 25 30 Asp GlyIle Arg Met Trp Phe Gln Trp Ser Glu Gln Arg Asp Tyr Ile 35 40 45 Asp ThrThr Trp Asn Cys Gly Tyr Leu Leu Ala Ser 50 55 60 313 17 PRT Homo sapiens313 Ala Ser Phe Leu Leu Ser Arg Thr Ser Trp Gly Thr Ala Leu Met Ile 1 510 15 Leu 314 8 PRT Homo sapiens 314 Leu Met Arg Asn Glu Ser Arg Ser 1 5315 13 PRT Homo sapiens 315 Ala Ser Phe Leu Leu Ser Arg Thr Ser Trp GlyThr Ala 1 5 10 316 17 PRT Homo sapiens 316 Ala Ser Phe Leu Leu Ser ArgThr Ser Trp Gly Thr Ala Leu Met Ile 1 5 10 15 Leu 317 72 PRT Homosapiens 317 Pro Ser Phe Thr Leu Thr Pro Ala Ser Phe Leu Leu Ser Arg ThrSer 1 5 10 15 Trp Gly Thr Ala Leu Met Ile Leu Val Ala Ile Gly Phe LysThr Lys 20 25 30 Leu Ala Ala Leu Thr Leu Val Val Trp Leu Phe Ala Ile AsnVal Tyr 35 40 45 Phe Asn Ala Phe Trp Thr Ile Pro Val Tyr Lys Pro Met HisAsp Phe 50 55 60 Leu Lys Tyr Asp Phe Phe Gln Thr 65 70 318 236 PRT Homosapiens MISC_FEATURE (115) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 318 Arg Thr Glu Pro Pro Pro GlyThr Ser Cys Gly Gly Arg Ser Gly Cys 1 5 10 15 Gly Arg Arg Arg Ala ArgAla Ser Glu Arg Ala Ser Glu Pro Ser Arg 20 25 30 Ala Ser Arg Arg Arg HisGly Pro Glu Arg Pro Asp Gly His Gly Arg 35 40 45 Gly Leu Arg Arg Pro ValPro Pro Cys His Lys Ala Val Pro Ala Pro 50 55 60 Arg Gly Ala Pro Leu SerAsp Gln His Leu Pro Gly Gly Arg His Pro 65 70 75 80 Tyr Val Val Pro ValGlu Arg Ala Ala Arg Leu His Arg His His Leu 85 90 95 Glu Leu Arg Leu ProAla Gly Leu Val Leu Arg Leu Pro Gln Leu Ala 100 105 110 Gly Thr Xaa ThrGly Cys Val Leu Val Leu Ser Arg Asn Phe Val Gln 115 120 125 Tyr Ala CysPhe Gly Leu Phe Gly Ile Ile Ala Leu Gln Thr Ile Ala 130 135 140 Tyr SerIle Leu Trp Asp Leu Lys Phe Leu Met Arg Asn Leu Ala Leu 145 150 155 160Gly Gly Gly Leu Leu Leu Leu Leu Ala Glu Ser Arg Ser Glu Gly Lys 165 170175 Ser Met Phe Ala Gly Val Pro Thr Met Arg Glu Ser Ser Pro Lys Gln 180185 190 Tyr Met Gln Leu Gly Gly Arg Val Leu Leu Val Leu Met Phe Met Thr195 200 205 Leu Leu His Phe Asp Ala Ser Phe Phe Ser Ile Val Gln Asn IleVal 210 215 220 Gly His Ser Ser Asp Asp Phe Ser Gly His Trp Phe 225 230235 319 114 PRT Homo sapiens MISC_FEATURE (2) Xaa equals any of theL-amino acids commonly found in naturally occurring proteins 319 Gly XaaSer Arg Arg Arg Ala Leu Pro Val Glu Ala Ala Ala Gly Ala 1 5 10 15 GlyAla Asp Gly Arg Glu Pro Ala Ser Glu Arg Ala Ser Arg Ala Glu 20 25 30 ProPro Ala Val Ala Met Gly Gln Asn Asp Leu Met Gly Thr Ala Glu 35 40 45 AspPhe Ala Asp Gln Phe Leu Arg Val Thr Lys Gln Tyr Leu Pro His 50 55 60 ValAla Arg Leu Cys Leu Ile Ser Thr Phe Leu Glu Asp Gly Ile Arg 65 70 75 80Met Trp Phe Gln Trp Ser Glu Gln Arg Asp Tyr Ile Asp Thr Thr Trp 85 90 95Asn Cys Gly Tyr Leu Leu Ala Ser Ser Phe Val Phe Leu Asn Leu Leu 100 105110 Gly Xaa 320 63 PRT Homo sapiens 320 Trp Val Phe Leu Phe Leu Leu AlaLeu Gly Gly Leu Gly Pro Asp Ser 1 5 10 15 Gly Arg Cys Leu Cys Arg GluGly Arg Ile Ser Gly Ile Tyr Gln Leu 20 25 30 Ile Leu Ala Lys Gln Phe LeuArg Phe Phe Cys Phe Met Trp Glu Thr 35 40 45 Asp Leu Asn Leu Ile Leu CysCys Ile Leu Tyr Leu Ser Cys Val 50 55 60 321 106 PRT Homo sapiens 321Ser Met Ser Ala Leu Thr Arg Leu Ala Ser Phe Ala Arg Val Gly Gly 1 5 1015 Arg Leu Phe Arg Ser Gly Cys Ala Arg Thr Ala Gly Asp Gly Gly Val 20 2530 Arg His Ala Gly Gly Gly Val His Ile Glu Pro Arg Tyr Arg Gln Phe 35 4045 Pro Gln Leu Thr Arg Ser Gln Val Phe Gln Ser Glu Phe Phe Ser Gly 50 5560 Leu Met Trp Phe Trp Ile Leu Trp Arg Phe Trp His Asp Ser Glu Glu 65 7075 80 Val Leu Gly His Phe Pro Tyr Pro Asp Pro Ser Gln Trp Thr Asp Glu 8590 95 Glu Leu Gly Ile Pro Pro Asp Asp Glu Asp 100 105 322 20 PRT Homosapiens 322 Phe Ile Ser Phe Ala Asn Ser Arg Ser Ser Glu Asp Thr Lys GlnMet 1 5 10 15 Met Ser Ser Phe 20 323 27 PRT Homo sapiens 323 Asp Pro ArgArg Pro Asn Lys Val Leu Arg Tyr Lys Pro Pro Pro Ser 1 5 10 15 Glu CysAsn Pro Ala Leu Asp Asp Pro Thr Pro 20 25 324 30 PRT Homo sapiens 324Asp Tyr Met Asn Leu Leu Gly Met Ile Phe Ser Met Cys Gly Leu Met 1 5 1015 Leu Lys Leu Lys Trp Cys Ala Trp Val Ala Val Tyr Cys Ser 20 25 30 32522 PRT Homo sapiens 325 Met Leu Ser Ile Ser Ala Val Val Met Ser Tyr LeuGln Asn Pro Gln 1 5 10 15 Pro Met Thr Pro Pro Trp 20 326 52 PRT Homosapiens MISC_FEATURE (35) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 326 Ala Ala Gly Asp Gly Asp ValLys Leu Gly Thr Leu Gly Ser Gly Ser 1 5 10 15 Glu Ser Ser Asn Asp GlyGly Ser Glu Ser Pro Gly Asp Ala Gly Ala 20 25 30 Ala Ala Xaa Gly Gly GlyTrp Ala Ala Ala Ala Leu Ala Leu Leu Thr 35 40 45 Gly Gly Gly Glu 50 32762 PRT Homo sapiens MISC_FEATURE (45) Xaa equals any of the L-aminoacids commonly found in naturally occurring proteins 327 Ser Thr His AlaSer Gly Arg Ala Val Met Ala Ala Gly Asp Gly Asp 1 5 10 15 Val Lys LeuGly Thr Leu Gly Ser Gly Ser Glu Ser Ser Asn Asp Gly 20 25 30 Gly Ser GluSer Pro Gly Asp Ala Gly Ala Ala Ala Xaa Gly Gly Gly 35 40 45 Trp Ala AlaAla Ala Leu Ala Leu Leu Thr Gly Gly Gly Glu 50 55 60 328 177 PRT Homosapiens MISC_FEATURE (26) Xaa equals any of the L-amino acids commonlyfound in naturally occurring proteins 328 Ala Ala Asp Asn Tyr Gly IlePro Arg Ala Cys Arg Asn Ser Ala Arg 1 5 10 15 Ser Tyr Gly Ala Ala TrpLeu Leu Leu Xaa Pro Ala Gly Ser Ser Arg 20 25 30 Val Glu Pro Thr Gln AspIle Ser Ile Ser Asp Gln Leu Gly Gly Gln 35 40 45 Asp Val Pro Val Phe ArgAsn Leu Ser Leu Leu Val Val Gly Val Gly 50 55 60 Ala Val Phe Ser Leu LeuPhe His Leu Gly Thr Arg Glu Arg Arg Arg 65 70 75 80 Pro His Ala Xaa GluPro Gly Glu His Thr Pro Leu Leu Ala Pro Ala 85 90 95 Thr Ala Gln Pro LeuLeu Leu Trp Lys His Trp Leu Arg Glu Xaa Ala 100 105 110 Phe Tyr Gln ValGly Ile Leu Tyr Met Thr Thr Arg Leu Ile Val Asn 115 120 125 Leu Ser GlnThr Tyr Met Ala Met Tyr Leu Thr Tyr Ser Leu His Leu 130 135 140 Pro LysLys Phe Ile Ala Thr Ile Pro Leu Val Met Tyr Leu Ser Gly 145 150 155 160Phe Leu Ser Ser Phe Leu Met Lys Pro Ile Asn Lys Cys Ile Gly Arg 165 170175 Asn 329 79 PRT Homo sapiens MISC_FEATURE (7) Xaa equals any of theL-amino acids commonly found in naturally occurring proteins 329 Cys ThrLeu Ala Met Trp Xaa Leu Gly His Cys Asp Pro Arg Arg Cys 1 5 10 15 ThrGly Arg Lys Leu Ala Arg Leu Gly Leu Val Arg Cys Leu Arg Leu 20 25 30 GlyHis Arg Phe Gly Gly Leu Val Leu Ser Pro Val Gly Lys Gln Tyr 35 40 45 AlaSer Pro Ala Asp Arg Gln Leu Val Ala Gln Ser Gly Val Ala Val 50 55 60 IleAsp Cys Ser Trp Ala Arg Leu Asp Glu Thr Pro Phe Gly Lys 65 70 75 330 72PRT Homo sapiens 330 Ser Gly Arg Gly Ala Arg Ser Asp Val Thr Ala Met AlaGly Ile Lys 1 5 10 15 Ala Leu Ile Ser Leu Ser Phe Gly Gly Ala Ile GlyLeu Met Phe Leu 20 25 30 Met Leu Gly Cys Ala Leu Pro Ile Tyr Asn Lys TyrTrp Pro Leu Phe 35 40 45 Val Leu Phe Phe Tyr Ile Leu Ser Pro Ile Pro TyrCys Ile Ala Arg 50 55 60 Arg Leu Val Asp Asp Thr Asp Ala 65 70 331 32PRT Homo sapiens MISC_FEATURE (5) Xaa equals any of the L-amino acidscommonly found in naturally occurring proteins 331 Ala Arg Val Arg XaaArg Gly Ala Leu Ser Leu Ser Val Gly Ala Ala 1 5 10 15 Cys Gly Leu ValAla Leu Trp Gln Arg Arg Arg Gln Asp Ser Gly Thr 20 25 30 332 45 PRT Homosapiens 332 Leu Ser Asn Asn Ala Gln Asn Trp Gly Met Gln Arg Ala Thr AsnVal 1 5 10 15 Thr Tyr Gln Ala His His Val Ser Arg Asn Lys Arg Gly GlnVal Val 20 25 30 Gly Thr Arg Gly Gly Phe Arg Gly Cys Thr Val Trp Leu 3540 45 333 38 PRT Homo sapiens 333 Val Ser Met Ala Leu Glu Glu Tyr LeuVal Cys His Gly Ile Pro Cys 1 5 10 15 Tyr Thr Leu Asp Gly Asp Asn IleArg Gln Gly Leu Asn Lys Asn Leu 20 25 30 Gly Phe Ser Pro Glu Asp 35 33439 PRT Homo sapiens 334 Thr Gln Asp Arg Asn Asn Ala Arg Gln Ile His GluGly Ala Ser Leu 1 5 10 15 Pro Phe Phe Glu Val Phe Val Asp Ala Pro LeuHis Val Cys Glu Gln 20 25 30 Arg Asp Val Lys Gly Leu Tyr 35 335 40 PRTHomo sapiens 335 Phe Thr Gly Ile Asp Ser Glu Tyr Glu Lys Pro Glu Ala ProGlu Leu 1 5 10 15 Val Leu Lys Thr Asp Ser Cys Asp Val Asn Asp Cys ValGln Gln Val 20 25 30 Val Glu Leu Leu Gln Glu Arg Asp 35 40 336 41 PRTHomo sapiens 336 Ala Glu Thr Leu Pro Ala Leu Lys Ile Asn Lys Val Asp MetGln Trp 1 5 10 15 Val Gln Val Leu Ala Glu Gly Trp Ala Thr Pro Leu AsnGly Phe Met 20 25 30 Arg Glu Arg Glu Tyr Leu Gln Cys Leu 35 40 337 30PRT Homo sapiens 337 Val Pro Ile Val Leu Thr Ala Thr His Glu Asp Lys GluArg Leu Asp 1 5 10 15 Gly Cys Thr Ala Phe Ala Leu Met Tyr Glu Gly ArgArg Val 20 25 30 338 39 PRT Homo sapiens 338 Ile Gly Gly Asp Leu Gln ValLeu Asp Arg Val Tyr Trp Asn Asp Gly 1 5 10 15 Leu Asp Gln Tyr Arg LeuThr Pro Thr Glu Leu Lys Gln Lys Phe Lys 20 25 30 Asp Met Asn Ala Asp AlaVal 35 339 37 PRT Homo sapiens 339 Gly His Ala Leu Leu Met Gln Asp ThrHis Lys Gln Leu Leu Glu Arg 1 5 10 15 Gly Tyr Arg Arg Pro Val Leu LeuLeu His Pro Leu Gly Gly Trp Thr 20 25 30 Lys Asp Asp Asp Val 35 340 41PRT Homo sapiens 340 Met Tyr Ala Gly Pro Thr Glu Val Gln Trp His Cys ArgAla Arg Met 1 5 10 15 Val Ala Gly Ala Asn Phe Tyr Ile Val Gly Arg AspPro Ala Gly Met 20 25 30 Pro His Pro Glu Thr Gly Lys Asp Leu 35 40 34134 PRT Homo sapiens 341 Leu Thr Met Ala Pro Gly Leu Ile Thr Leu Glu IleVal Pro Phe Arg 1 5 10 15 Val Ala Ala Tyr Asn Lys Lys Lys Lys Arg MetAsp Tyr Tyr Asp Ser 20 25 30 Glu His 342 19 PRT Homo sapiens 342 Gly PheMet Ala Pro Lys Ala Trp Thr Val Leu Thr Glu Tyr Tyr Lys 1 5 10 15 SerLeu Glu 343 243 PRT Homo sapiens MISC_FEATURE (30) Xaa equals any of theL-amino acids commonly found in naturally occurring proteins 343 Arg IleThr Asp Asn Pro Glu Gly Lys Trp Leu Gly Arg Thr Ala Arg 1 5 10 15 GlySer Tyr Gly Tyr Ile Lys Thr Thr Ala Val Glu Ile Xaa Tyr Asp 20 25 30 SerLeu Lys Leu Lys Lys Asp Ser Leu Gly Ala Pro Ser Arg Pro Ile 35 40 45 GluAsp Asp Gln Glu Val Tyr Asp Asp Val Ala Glu Gln Asp Asp Ile 50 55 60 SerSer His Ser Gln Ser Gly Ser Gly Gly Ile Phe Pro Pro Pro Pro 65 70 75 80Asp Asp Asp Ile Tyr Asp Gly Ile Glu Glu Glu Asp Ala Asp Asp Gly 85 90 95Phe Pro Ala Pro Pro Lys Gln Leu Asp Met Gly Asp Glu Val Tyr Asp 100 105110 Asp Val Asp Thr Ser Asp Phe Pro Val Ser Ser Ala Glu Met Ser Gln 115120 125 Gly Thr Asn Val Gly Lys Ala Lys Thr Glu Glu Lys Asp Leu Lys Lys130 135 140 Leu Lys Lys Gln Xaa Lys Glu Xaa Lys Asp Phe Arg Lys Lys PheLys 145 150 155 160 Tyr Asp Gly Glu Ile Arg Val Leu Tyr Ser Thr Lys ValThr Thr Ser 165 170 175 Ile Thr Ser Lys Lys Trp Gly Thr Arg Asp Leu GlnVal Lys Pro Gly 180 185 190 Glu Ser Leu Glu Val Ile Gln Thr Thr Asp AspThr Lys Val Leu Cys 195 200 205 Arg Asn Glu Glu Gly Lys Tyr Gly Tyr ValLeu Arg Ser Tyr Leu Ala 210 215 220 Asp Asn Asp Gly Glu Ile Tyr Asp AspIle Ala Asp Gly Cys Ile Tyr 225 230 235 240 Asp Asn Asp

What is claimed is:
 1. An isolated nucleic acid molecule comprising apolynucleotide having a nucleotide sequence at least 95% identical to asequence selected from the group consisting of: (a) a polynucleotidefragment of SEQ ID NO:X or a polynucleotide fragment of the cDNAsequence included in ATCC Deposit No:Z, which is hybridizable to SEQ IDNO:X; (b) a polynucleotide encoding a polypeptide fragment of SEQ IDNO:Y or a polypeptide fragment encoded by the cDNA sequence included inATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X; (c) apolynucleotide encoding a polypeptide domain of SEQ ID NO:Y or apolypeptide domain encoded by the cDNA sequence included in ATCC DepositNo:Z, which is hybridizable to SEQ ID NO:X; (d) a polynucleotideencoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitopeencoded by the cDNA sequence included in ATCC Deposit No:Z, which ishybridizable to SEQ ID NO:X; (e) a polynucleotide encoding a polypeptideof SEQ ID NO:Y or the cDNA sequence included in ATCC Deposit No:Z, whichis hybridizable to SEQ ID NO:X, having biological activity; (f) apolynucleotide which is a variant of SEQ ID NO:X; (g) a polynucleotidewhich is an allelic variant of SEQ ID NO:X; (h) a polynucleotide whichencodes a species homologue of the SEQ ID NO:Y; (i) a polynucleotidecapable of hybridizing under stringent conditions to any one of thepolynucleotides specified in (a)-(h), wherein said polynucleotide doesnot hybridize under stringent conditions to a nucleic acid moleculehaving a nucleotide sequence of only A residues or of only T residues.2. The isolated nucleic acid molecule of claim 1, wherein thepolynucleotide fragment comprises a nucleotide sequence encoding asecreted protein.
 3. The isolated nucleic acid molecule of claim 1,wherein the polynucleotide fragment comprises a nucleotide sequenceencoding the sequence identified as SEQ ID NO:Y or the polypeptideencoded by the cDNA sequence included in ATCC Deposit No:Z, which ishybridizable to SEQ ID NO:X.
 4. The isolated nucleic acid molecule ofclaim 1, wherein the polynucleotide fragment comprises the entirenucleotide sequence of SEQ ID NO:X or the cDNA sequence included in ATCCDeposit No:Z, which is hybridizable to SEQ ID NO:X.
 5. The isolatednucleic acid molecule of claim 2, wherein the nucleotide sequencecomprises sequential nucleotide deletions from either the C-terminus orthe N-terminus.
 6. The isolated nucleic acid molecule of claim 3,wherein the nucleotide sequence comprises sequential nucleotidedeletions from either the C-terminus or the N-terminus.
 7. A recombinantvector comprising the isolated nucleic acid molecule of claim
 1. 8. Amethod of making a recombinant host cell comprising the isolated nucleicacid molecule of claim
 1. 9. A recombinant host cell produced by themethod of claim
 8. 10. The recombinant host cell of claim 9 comprisingvector sequences.
 11. An isolated polypeptide comprising an amino acidsequence at least 95% identical to a sequence selected from the groupconsisting of: (a) a polypeptide fragment of SEQ ID NO:Y or the encodedsequence included in ATCC Deposit No:Z; (b) a polypeptide fragment ofSEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z,having biological activity; (c) a polypeptide domain of SEQ ID NO:Y orthe encoded sequence included in ATCC Deposit No:Z; (d) a polypeptideepitope of SEQ ID NO:Y or the encoded sequence included in ATCC DepositNo:Z; (e) a secreted form of SEQ ID NO:Y or the encoded sequenceincluded in ATCC Deposit No:Z; (f) a full length protein of SEQ ID NO:Yor the encoded sequence included in ATCC Deposit No:Z; (g) a variant ofSEQ ID NO:Y; (h) an allelic variant of SEQ ID NO:Y; or (i) a specieshomologue of the SEQ ID NO:Y.
 12. The isolated polypeptide of claim 11,wherein the secreted form or the full length protein comprisessequential amino acid deletions from either the C-terminus or theN-terminus.
 13. An isolated antibody that binds specifically to theisolated polypeptide of claim
 11. 14. A recombinant host cell thatexpresses the isolated polypeptide of claim
 11. 15. A method of makingan isolated polypeptide comprising: (a) culturing the recombinant hostcell of claim 14 under conditions such that said polypeptide isexpressed; and (b) recovering said polypeptide.
 16. The polypeptideproduced by claim
 15. 17. A method for preventing, treating, orameliorating a medical condition, comprising administering to amammalian subject a therapeutically effective amount of the polypeptideof claim 11 or the polynucleotide of claim
 1. 18. A method of diagnosinga pathological condition or a susceptibility to a pathological conditionin a subject comprising: (a) determining the presence or absence of amutation in the polynucleotide of claim 1; and (b) diagnosing apathological condition or a susceptibility to a pathological conditionbased on the presence or absence of said mutation.
 19. A method ofdiagnosing a pathological condition or a susceptibility to apathological condition in a subject comprising: (a) determining thepresence or amount of expression of the polypeptide of claim 11 in abiological sample; and (b) diagnosing a pathological condition or asusceptibility to a pathological condition based on the presence oramount of expression of the polypeptide.
 20. A method for identifying abinding partner to the polypeptide of claim 11 comprising: (a)contacting the polypeptide of claim 11 with a binding partner; and (b)determining whether the binding partner effects an activity of thepolypeptide.
 21. The gene corresponding to the cDNA sequence of SEQ IDNO:Y.
 22. A method of identifying an activity in a biological assay,wherein the method comprises: (a) expressing SEQ ID NO:X in a cell; (b)isolating the supernatant; (c) detecting an activity in a biologicalassay; and (d) identifying the protein in the supernatant having theactivity.
 23. The product produced by the method of claim 22.